Comparing Allogeneic vs. Autologous Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia - Evaluating Outcomes Across Age Groups: A Systematic Review

doi:10.21203/rs.3.rs-4965995/v1

Download PDF

Systematic Review

Comparing Allogeneic vs. Autologous Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia - Evaluating Outcomes Across Age Groups: A Systematic Review

https://doi.org/10.21203/rs.3.rs-4965995/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Acute myeloid leukaemia (AML) impacts various age groups, with hematopoietic stem cell transplantation (HSCT) being an important treatment option, this review compares the outcomes of allogeneic and autologous HSCT, focusing on the influencing factors across different age demographics.

Methods

A comprehensive literature search was conducted across five databases, including PubMed/Medline, Cochrane Library, ScienceDirect, Europe PMC, EBSCO, and ClinicalTrials.gov. The inclusion criteria encompassed randomized controlled trials (RCTs), non-randomized controlled trials, cohort studies, and case-control studies published since inception. After screening, 19 studies were selected for review, all demonstrating moderate to high quality.

Results

A total of 21,977 participants were included across the 19 studies, the majority of which were observational. Key outcomes assessed post-transplantation included overall survival (OS), disease-free survival (DFS), relapse rates, transplant-related mortality (TRM), and relapse-free survival (RFS). Notably, patients with abnormal 17p chromosomes exhibited varying OS based on age, with those under 50 showing better outcomes. An RCT indicated that autologous HSCT resulted in lower TRM and improved OS for children and adolescents, albeit with higher relapse rates compared to allogeneic HSCT. In elderly populations, autologous HSCT showed no significant difference in OS but demonstrated lower non-relapse mortality (NRM) compared to allogeneic HSCT.

Conclusion

Various factors influence HSCT outcomes in AML patients. Autologous HSCT may yield better results for children and adolescents, while allogeneic HSCT appears more effective for adults and the elderly concerning survival and relapse rates, despite some studies indicating a mortality advantage for autologous HSCT.

Acute myeloid leukaemia (AML) is a haematological malignancy that primarily affects the elderly population, although it is also observed in young adults and children. Among paediatric patients, a rare subtype known as acute promyelocytic leukaemia constitutes approximately 4-8% of the AML cases in the United States [1,2]. Patients diagnosed with AML present with a diverse array of symptoms, including weight loss, night sweats, anaemia, recurrent infections, bleeding manifestations, and lymphadenopathy [27].

Current treatment modalities encompass a combination of chemotherapy, targeted therapies, stem cell transplantation, and growth factors. Notably, allogeneic hematopoietic stem cell transplantation has emerged as a highly effective treatment option for both children and adults afflicted with AML [27]. However, various factors, such as age, sex, the presence of anti-HLA antibodies, and different chromosomal mutations, significantly influence overall survival, disease-free survival, relapse rates, and mortality outcomes [3,4,5].

Recent research has sparked interest in determining the comparative advantages of autologous versus allogeneic hematopoietic stem cell transplantation across different age demographics in AML patients. Studies indicate that autologous HSCT yields favourable prognostic outcomes for the paediatric population [1,6]. Conversely, young adults and elderly patients are increasingly receiving allogeneic HSCT on a large scale [7,8].

Given the variability in treatment responses among different age groups, it is imperative to ascertain which type of HSCT is most beneficial for specific patient demographics. Therefore, the objective of this study is to analyse which age group derives the greatest benefit from either autologous or allogeneic HSCT.

2.1 Search Strategy

Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 [9], a comprehensive literature search was conducted across PubMed/Medline, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Europe PMC, ClinicalTrials.gov, and EBSCO Open Dissertations from June 26 to July 2, 2024, to compare the efficacy of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) in acute myeloid leukaemia (AML) patients regarding overall survival (OS), relapse-free survival (RFS), and transplant-related mortality (TRM) across different age groups.

Twenty-three keywords were initially identified through a background search and subsequently employed to develop a PubMed/Medline search strategy utilizing both full-text and Medical Subject Headings (MeSH)terms (Table 1). This strategy was adapted for the remaining databases.

Table 1

Search Strategy
Search Strategy	Databases/Registers	Number of studies before and after filters	Filters used
"Allogeneic hematopoietic stem cell transplant" OR "Allogeneic HSCT" OR "Allogeneic bone marrow transplant" OR "Allogeneic BMT" OR "Myeloablative allogeneic HSCT" OR "Myeloablative allogeneic Hematopoietic stem cell transplant" OR "Autologous hematopoietic stem cell transplant" OR "Autologous HSCT" OR "Autologous bone marrow transplant" OR "Autologous BMT" OR "Myeloablative Autologous HSCT" OR "Myeloablative Autologous Hematopoietic stem cell transplant" AND "Acute myeloid leukemia" OR "AML" OR "Acute granulocytic leukemia" OR "Acute myelocytic leukemia" OR "Acute myelogenous leukemia" OR "Acute non-lymphocytic leukemia" OR ( "Leukemia, Myeloid, Acute/mortality"[Mesh] OR "Leukemia, Myeloid, Acute/therapy"[Mesh] ) AND "Overall Survival" OR "Relapse-Free Survival" OR "RFS" OR "transplant-related mortality" OR "TRM"	Pubmed/Medline	375/62	Filters applied: Full text, Clinical Study, Clinical Trial, Observational Study, Randomized Controlled Trial, Humans, English.
#1"Allogeneic NEAR hematopoietic NEAR stem cell transplant" OR "Allogeneic HSCT" OR "Allogeneic NEAR bone marrow NEAR transplant" OR "Allogeneic BMT" OR "Myeloablative NEAR allogeneic HSCT" OR "Myeloablative allogeneic NEAR Hematopoietic NEAR stem cell transplant" #2"Autologous hematopoietic stem cell transplant" OR "Autologous HSCT" OR "Autologous bone marrow transplant" OR "Autologous BMT" OR "Myeloablative Autologous HSCT" OR "Myeloablative Autologous Hematopoietic stem cell transplant" #3#1 OR #2 #4"Acute myeloid leukemia" OR "AML" OR "Acute granulocytic leukemia" OR "Acute myelocytic leukemia" OR "Acute myelogenous leukemia" OR "Acute non-lymphocytic leukemia" #5MeSH descriptor: [Leukemia, Myeloid, Acute] explode all trees #6#4 OR #5 #7"Overall Survival" OR "Relapse-Free Survival" OR "RFS" OR "transplant-related mortality" OR "TRM" #8MeSH descriptor: [Survival] this term only #9MeSH descriptor: [Recurrence] explode all trees #10#7 OR #8 OR # 9 #11#3 AND #6 AND #10	Cochrane Library (CENTRAL)	119/105	English, only Clinical trials excluding reviews, protocols, editorials, clinical answers.
"Acute myeloid leukemia" OR "AML" OR "Acute granulocytic leukemia" OR "Acute myelocytic leukemia" OR "Acute myelogenous leukemia" OR "Acute non-lymphocytic leukemia" \| "Allogeneic hematopoietic stem cell transplant" OR "Allogeneic HSCT" OR "Allogeneic bone marrow transplant" OR "Allogeneic BMT" OR "Myeloablative allogeneic HSCT" OR "Myeloablative allogeneic Hematopoietic stem cell transplant" OR "Autologous hematopoietic stem cell transplant" OR "Autologous HSCT" OR "Autologous bone marrow transplant" OR "Autologous BMT" OR "Myeloablative Autologous HSCT" OR "Myeloablative Autologous Hematopoietic stem cell transplant" \| Completed studies \| Interventional, Observational studies \| Studies with results \| Outcome measure: "Overall Survival" OR "Relapse-Free Survival" OR "RFS" OR "transplant-related mortality" OR "TRM"	ClinicalTrials,gov Register	87/27	Completed studies \| Interventional, Observational studies \| Studies with results \| Outcome measure: "Overall Survival" OR "Relapse-Free Survival" OR "RFS" OR "transplant-related mortality" OR "TRM"
"Acute myeloid leukemia" AND "Overall survival" OR "Allogeneic hematopoietic stem cell transplant" OR "Autologous hematopoietic stem cell transplant" NOT "Review"	EBSCO	23/23	Dissertations
"Acute myeloid leukemia" AND "Allogeneic hematopoietic stem cell transplant" OR "Autologous hematopoietic stem cell transplant" AND "Overall Survival	Science direct	1866/247	Research articles Medicine and Dentistry English Open access & Open archive Search strategy in Title/abstract
(("Acute myeloid leukemia" OR "AML" OR "Acute granulocytic leukemia" OR "Acute myelocytic leukemia" OR "Acute myelogenous leukemia" OR "Acute non-lymphocytic leukemia") AND ("Allogeneic hematopoietic stem cell transplant" OR "Allogeneic HSCT" OR "Allogeneic bone marrow transplant" OR "Allogeneic BMT" OR "Myeloablative allogeneic HSCT" OR "Myeloablative allogeneic Hematopoietic stem cell transplant") OR ("Autologous hematopoietic stem cell transplant" OR "Autologous HSCT" OR "Autologous bone marrow transplant" OR "Autologous BMT" OR "Myeloablative Autologous HSCT" OR "Myeloablative Autologous Hematopoietic stem cell transplant") AND ("Overall Survival" OR "Relapse-Free Survival" OR "RFS" OR "transplant-related mortality" OR "TRM")) AND (HAS_FT:Y) AND (((SRC:MED OR SRC:PMC OR SRC:AGR OR SRC:CBA) NOT (PUB_TYPE:"Review")))	Europe PMC	927/546	Research articles, Full text

Studies were included if they met the criteria as follows: participants were patients with AML; study designs encompassed RCTs, non-randomized controlled trials, cohort studies, or case-control studies; interventions involved allogeneic or autologous hematopoietic stem cell transplantation (HSCT); outcomes reported overall survival (OS), relapse-free survival (RFS), or transplant-related mortality (TRM) and studies were published in English (Table 2).

Table 2

Inclusion and Exclusion Criteria for Study Selection
INCLUSION CRITERIA	EXCLUSION CRITERIA
Patients with AML	Patients with chronic leukaemia, acute lymphoblastic leukaemia or other haematological malignancies
RCTs, non-randomized controlled trials, Cohort studies, or Case-control studies	Case reports, Case series, Reviews, Meta-analyses, or Expert opinions
Studies from registers which are completed and have results	Studies from registers if incomplete or ongoing or complete but without results
Interventions involved allogeneic or autologous HSCT	If interventions did not involve allogeneic or autologous HSCT for AML
Outcomes reported OS, RFS, or TRM	Outcomes did not report OS, RFS, or TRM
Published in English	Published in other languages
Studies published from inception till July 22, 2024	Studies published after search strategy was concluded (July 22, 2024)

AML (Acute myeloid leukaemia), RCTs (Randomised controlled trials), HSCT Hematopoietic stem cell transplantation), OS (Overall survival), RFS (Relapse-free survival), TRM (Transplant related mortality)

2.2 Screening and Quality Assessment:

A rigorous two-stage screening process was employed, utilizing the Rayyan app ® [10] for initial record management. Initially, a single reviewer screened titles and abstracts to identify potentially relevant studies. Subsequently, two independent reviewers assessed full-text articles against the inclusion and exclusion criteria. Disagreements were resolved through consensus or arbitration by a third reviewer.

To evaluate study quality, the Newcastle-Ottawa Scale (NOS) was applied to observational studies [11], the ROBINS-I tool [12] to non-randomized clinical trials, and the Cochrane Risk-of-Bias tool (RoB 2) [13] to randomized controlled trials. Two independent reviewers assessed study quality, with discrepancies resolved through consensus or arbitration. Studies were categorized as having good, fair, or poor quality based on the overall risk of bias assessment.

2.3 Data synthesis

The extracted data was synthesized according to the study designs and outcome measures of the included research. Due to the anticipated heterogeneity in methodologies and designs, a narrative synthesis approach was utilized to effectively summarize and interpret the findings.

The PRISMA flow diagram (Fig. 1) demonstrates the screening process done in order to include the 19 studies for review.

Figure 1. PRISMA Flow Diagram

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

The systematic search, guided by the search strategy elaborated upon in the methods section, yielded a total of 3,397 studies from the targeted databases and registry. Applying predefined filters resulted in the exclusion of 2,387 studies, with a further 149 duplicates removed. Following this initial screening, studies were meticulously assessed against the inclusion and exclusion criteria detailed in Table 2. This evaluation led to the exclusion of an additional 698 studies. These excluded studies encompassed those with research populations that differed from the target population, employed case report or case series designs (which fell outside the scope of this review), involved interventions beyond the focus on gut microbiota evaluation, or were ongoing studies lacking reported results.

This rigorous selection process yielded 162 studies for potential retrieval. However, limitations in full-text availability resulted in the inability to retrieve 59 of these studies. The remaining 102 papers underwent further evaluation based on their relevance to the research question. Reasons for exclusion at this stage included investigating outcomes outside the predefined scope of the review (e.g., outcomes not related to overall survival, mortality, relapse), employing additional interventions beyond the evaluation of gut microbiota, lacking complete data due to only having abstracts available, or being completed clinical trials without reported results.

Following this comprehensive selection process, 19 studies were identified for further quality assessment.

3.1 Risk of Bias Assessment

The NOS scale [11] was employed to assess the quality of the 14 observational studies included in the review. The NOS focuses on three key areas: selection of study groups, comparability between the study and control groups, and assessment of the study outcomes. Each study received a score ranging from zero to nine points. Studies deemed acceptable for inclusion in the review achieved a score of at least seven out of nine points (equivalent to 77%). All 14 observational studies met this criterion and were subsequently included in the review process. Table 3 summarizes the detailed quality assessment results for these studies.

Table 3

Quality Assessment of Observational Studies: Newcastle-Ottawa Scale Scores
Study/ Year	Selection	Comparability	Outcome	Overall
Chang et al., 2021 [ ]	*******	**	*******	********
Mori et al., 2017 [ ]	*******	**	*******	********
Nampoothiri et al., 2021 [ ]	*******	**	*******	********
Tamaki et al., 2021 [ ]	*******	**	*******	********
Middeke et al., 2014 [ ]	*******	**	*******	********
Kongtim et al., 2015 [ ]	*******	**	*******	********
Narayan et al., 2023 [ ]	*******	**	*******	********
Hansen et al., 2021 [ ]	*******	**	*******	********
Sengsayadeth et al., 2018 [ ]	*******	**	*******	********
Armand et al., 2008 [ ]	*******	**	*******	********
Park et al., 2019 [ ]	*******	**	*******	********
Chien et al., 2021 [ ]	*******	**	*******	********
Locatelli et al., 2003 [ ]	*******	**	*******	********
Rao et al., 2017 [ ]	********	**	*******	*********

Note: A maximum of four stars (*) could be awarded for selection, two for comparability, and three for outcome domains. The total score ranges from zero to nine.

The RoB 2 assessment tool [13] was utilized to evaluate the risk of bias within the sole RCT included in this review [1]. The overall risk of bias judgment for this study was classified as "Some concerns."

The rationale for this classification stemmed from a lack of detailed information regarding blinding of participants, personnel, and outcome assessors. Additionally, the absence of a pre-specified analysis plan introduced some level of uncertainty. However, the study appeared to manage missing data effectively, and the reported outcomes aligned with the primary measures of interest (Table 4).

Table 4

Risk of Bias Assessment of Randomized Clinical Trials: Cochrane Risk-of-Bias Tool (RoB 2)
Study by /Year of Publication	Domain 1	Domain 2	Domain 3	Domain 4	Domain 5	Overall
Dvorak et al., 2008 [ ]	+	!	+	+	!	!

Note: RoB 2 domains: 1) Randomization process, 2) Deviations from intended interventions, 3) Missing outcome data, 4) Measurement of outcome, 5) Selection of reported result.

+, low risk of bias; -, high risk of bias; some concerns about risk of bias.

To ensure the exclusion of studies with a high risk of bias and to include only those with either low or some risk of bias, we incorporated the RCT by Dvorak et al. [1] in the future review. This approach was taken to minimize bias while maintaining a comprehensive evidence base for the review.

Among the four included non-randomized studies evaluated using the ROBINS-I tool, two studies [2, 3] exhibited some concerns regarding risk of bias. While these studies attempted to adjust for confounding factors, the potential influence of unmeasured confounders remains a concern (Table 5).

Table 5

Risk of Bias Assessment: Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) Tool
Study/Year	Domain 1	Domain 2	Domain 3	Domain 4	Domain 5	Domain 6	Domain 7	Overall
Detrait et al., 2018 [ 3 ]	!	+	+	+	+	!	+	!
Schlenk et al., 2010 [2 ]	!	+	+	+	+	!	+	!
Cho et al., 2021 [ 8]	+	+	+	+	+	+	+	+
Kümpers et al., 2018 [14 ]	+	+	+	+	+	+	+	+

Note: ROBINS-I domains: 1) Bias arising from confounding, 2) Bias arising from selection of participants, 3) Bias arising from classification of interventions, 4) Bias arising from deviations from intended interventions, 5) Bias arising from missing data, 6) Bias in measurement of outcomes, 7) Bias in selection of reported results.

+, low risk of bias; -, high risk of bias; !, some concerns about risk of bias.

Furthermore, unclear information regarding deviations from the intended intervention [2] and the lack of blinding for outcome assessors in all three studies raise additional concerns. Despite these limitations, these studies provide valuable information; however, the identified potential biases should be considered when interpreting their findings from these three studies specifically.

3.2 Characteristics of Included Studies

Our systematic review encompasses a total of 19 studies, including 14 observational studies, one RCT, and four clinical trials. The age range of participants spans from 0.5 years to 80 years, with a median age of approximately 55 years across the studies. Sample sizes vary significantly, with a minimum of 63 and a maximum of 10,923 participants.

Across the included studies, the most prevalent aim was to evaluate overall survival (OS) and disease-free survival (DFS) following HSCT in patients with AML. Many studies sought to compare outcomes between allogeneic and autologous HSCT, particularly focusing on how these outcomes vary across different age groups and cytogenetic risk categories.

The most reported measured outcome across these studies was overall survival (OS), followed closely by disease-free survival (DFS). Other commonly measured outcomes included non-relapse mortality (NRM), relapse rates, and transplant-related mortality (TRM). These outcomes provide critical insights into the effectiveness and safety of HSCT in treating AML.

Notably, factors such as age, cytogenetic risk, and pre-transplant conditions significantly influence survival outcomes, highlighting the need for tailored treatment approaches based on patient demographics and disease characteristics (Table 6).

Table 6

Summary of Included Studies.
Author/Year	Type of Study	Sample size	Median Age/ Age range	Aim of study	Key findings
Chang TY et al., 2021 [15 ]	Retrospective cohort study	63	6.3( 15–29)	To determine 5-year OS and DFS among adolescent and young adults (AYAs) and children with AML following allogeneic HSCT.	No significant difference in OS (p-value = 0.876) and in DFS (p-value = 0.833)
Mori, J et al., 2017 [4 ]	Retrospective cohort study	10923	Patients with abnormality in 17p = 53(15–80) Patients with no abnormality in 17p = 46(15–85)	To determine the OS, DFS, NRM and disease relapse in patients of AML with abnormalities in 17p chromosome across all cytogenetic risk categories when compared to patients with no abnormal 17p, post allogeneic HSCT	In poor cytogenetic risk group significant difference was observed in 5- year OS (p-value < 0.001), disease relapse (p -value < 0.001) and DFS (p-value < 0.001) In the intermediate risk group no significant risk was observed in OS (p-value = 0.2), DFS(p-value = 0.35), disease relapse (p-value = 0.71). No significant difference is observed in NRM in either poor or intermediate risk groups ( p-values = 0.648, 0.141 respectively).
Nampoothiri, R. V et al., 2021[ 16]	Retrospective cohort study	68	55	To evaluate the prognostic impact of UC or inconclusive cytogenetic analysis on outcomes in AML patients receiving allogeneic HSCT	Survival Outcomes: Relapse-Free Survival: No significant difference (UC: 66 months vs. normal: 42 months; p = 0.53). Overall Survival: Similar results (UC: 77 months vs. normal: 76 months; p = 0.72). Predictors of Overall Survival: Increased age at Allo HSCT (HR = 1.049). Favorable mutation profile (NPM1Mut/FLT3wt) (HR = 0.11). Neutrophil engraftment < 17 days. No chronic graft-versus-host disease (HR = 3.27).
Tamaki, M et al., 2021[17 ]	Retrospective cohort study	182	44 (15–69)	To determine the effect of high loss of body weight(LBW) vs low LBW prior to the start of transplantation on the NRM and OS post transplantation.	2-year OS and NRM are inferior in the high LBW group compared to low LBW group (p-value = 0.02 and 0.0025) Cumulative incidence of relapse was equal in both groups(p-value = 0.35) Age no effect on LBW(p-value = 0.2)
Middeke JM et al., 2014[5]	Retrospective cohort study	201	54 (2–75)	To determine the outcome of patients with abnormal 17p chromosomes after allogeneic HSCT.	OS% (p-value = 0.029): Age < 40 = 20 Age 40–50 = 23 Age 50–60 = 10 Age > 60 = 10 No significant difference in the NRM (p-value = 0.2)
Kongtim P et al., 2014[18 ]	Retrospective cohort study	841	50 (18–74)	To compare the NRM and ReR post allogeneic HSCT in F-M vs other gender combinations.	Significantly lower ReR(34.1 vs 41.3, p-value = 0.044) Significantly higher NRM(23.2 vs 15.7, p-value = 0.004) Patients age < 50 years have significantly higher ReR( p-value = 0.045) and no difference in NRM(p-value = 0.141)
Chien SH et al., 2021 [19 ]	Retrospective cohort study	1020	58 (18–80)	To compare the OS and DFS in SBHA and non-SBHA groups	Significant difference in OS and risk of relapse ( p-value = 0.028 and 0.015) No significant difference in DFS
Narayan R et al., 2023 [20]	Retrospective cohort study	255	57 (53–61)	To determine the OS in elderly patients with AML undergoing allogeneic HSCT based on CCI	Inferior OS in CCI >/= 3 (HR = 1.88, p-value = 0.001)
Hansen DK et al., 2020 [21 ]	Retrospective cohort study	500	55(18–76)	To determine the OS, LFS and relapse in the favorable, intermediate and adverse 2017 ELN risk groups	2-year OS was significantly higher in the favorable ELN 2017 risk group vs intermediate or adverse risk group (p-value = 0.03 and < 0.001) LFS was worse in the intermediate and the adverse risk group (p-value = 0.03 an d < 0.001) Relapse was higher in the adverse risk group(p-value = 0.006)
Sengsayadeth S et al., 2018 [7]	Retrospective cohort study	4997	58(50–64)	To determine OS, LFS and GRFS in patients with secondary AML post allogeneic HSCT	OS = 44.5% (95% CI, 43–46%) LFS = 38.8% (95% CI, 37.4–40.3%) GRFS = 27.2% (95% CI, 25.9–28.6%)
Armand P et al., 2008 [22 ]	Retrospective cohort study	445	45(18–71)	To generate a prognostic score based on age, disease, stage at transplantation, pretransplantation ferritin and cytogenetics to help divide patients into low, intermediate and high risk groups	Age < 40 is associated with low risk and is given a score of 0 whereas age>/= 40 is given a score of 1. Final score of </=2 is low risk group, = 3 is intermediate risk and >/=4 is high risk. OS %: Low risk group: 56% (48–64) Intermediate risk group: 22% (10–33) High risk group: 5% (0–12)
Park SS et al., 2018 [23 ]	Retrospective cohort study	324	49( 18–69)	To determine the GRFS, OS, DFS, TRM, Relapse at 3 years in patients undergoing allogeneic HSCT	GRFS = 34.5% (95% CI, 29.2 to 39.9) OS = 62.4% (95% CI, 56.7 to 67.6) DFS = 58.8% (95% CI, 53.1 to 64.1) TRM = 19.7% (95% CI, 15.5 to 24.3) Relapse = 21.1% (95% CI, 16.7 to 25.8) GRFS% at 3 years in patients age </= 37 vs > 37 (40.8 vs 28.7, p-value = 0.025)
Rao K et al., 2007 [24 ]	Retrospective cohort study	1739	Urban = 43 Rural = 46	To determine whether area of primary incidence has an effect on OS in patients with AML post either autologous or allogeneic HSCT.	In autologous HSCT group: Rural vs urban 5 year OS%= 48% vs 54%(p-value = 0.012) In the allogeneic HSCT group, the OS could not be determined.
Locatelli F et al., 2003 [6 ]	Retrospective cohort study	387	7.8 (0.5–16.0)	To evaluate factors which influence outcomes and study the incidence of long-term complications which occur in children who underwent autologous stem cell transplantation HSCT for AML in first CR.	5-Year TRM: 3% 5-Year Relapse Rate: 39% 5-Year LFS: 60% Overall Survival: 65% PBPCs and the BAVC preparative regimen were shown to have association with faster neutrophil recovery. Young age and absence of marrow purging predicted accelerated platelet reconstitution. Increased relapse probability was linked to the BAVC regimen, while in vitro purging of hematopoietic progenitors decreased relapse risk.
Dvorak CC et al., 2008 [1]	Randomized controlled trial	32(11 autologous HSCT and 12 allogeneic HSCT)	11 (1–16)	To compare the OS, TRM and ReR in children with acute promyelocytic leukemia receiving autologous HSCT vs allogeneic HSCT	Autologous vs Allogeneic HSCT: TRM = 0% vs 19% OS = 82% vs 76% (p-value = 1) ReR = 27% vs 10%
Schlenk RF et al., 2010 [2 ]	Clinical trial	267	48(16–62)	To measure the impact of matched related(MRD) and unrelated(MUD) donor HSCT in patients with high risk AML vs haploidentical donors or cord blood transplantation.	HSCT vs Non-HSCT recipients: OS%= 6.5% vs 25.1% No difference in outcome between allogeneic HSCT received from MRD and MUD
Detrait, M et al., 2012 [ 3]	Clinical trial	107	56 (19–67)	To compare the OS and TRM in patients of AML who received allogeneic HSCT on the basis of presence of anti-HLA antibodies	Anti-HLA + vs - 3-year OS%= 34% vs 16% (p-value = 0.006) A higher TRM was seen in Anti-HLA + positive patients, but it was not clinically significant
Cho BS et al., 2021 [ 8]	Clinical trial	154	63 (60–74)	To compare the OS, NRM in patients receiving matched related(MRD) or unrelated(MUD) donor HSCT or haplo-HSCT or autologous HSCT	No significant difference in OS in these groups. However the NRM is lower in the autologous HSCT group(18.2) when compared to allogeneic HSCT (32.2).
Kümpers, P et al., 2008 [14 ]	Clinical trial	90	54(19.1–71.2)	To determine the DFS on the basis of angiopoietin-2 (Ang-2)levels in patients with AML, post allogeneic HSCT.	The low Ang-2 group has a DFS% of 54% compared to 0% in the high Ang- 2 group
OS (Overall survival), DFS (Disease free survival), NRM (Non relapse mortality), CR ( Complete Remission), HSCT (Hematopoietic stem cell transplantation), ReR(Relapse rate), F-M (Males who received allogeneic HSCT from female donors), SBHA(Predicted strong binding HLA class 1 genotype to mutated NPM1), UC (Unclassified), non-SBHA (Predicted non strong binding HLA class 1 genotype to mutated NPM1), CCI(Charlson comorbidity index), HR(Hazard’s ratio), LFS(Leukemia free survival), ELN (European Leukemia Net), GRFS (GVHD-free, relapse-free survival), TRM (Transplant related mortality),PBPCs ( peripheral blood progenitor cells), BAVC (four chemotherapy agents: BCNU (N,N-bis[2-chloroethyl]-N-nitrosourea), Amsacrine, VP-16 (Etoposide), Cytosine Arabinoside)

This systematic review, conducted in accordance with the PRISMA 2020 guidelines [9], aimed to compare the outcomes of allogeneic versus autologous hematopoietic stem cell transplantation (HSCT) regarding survival, relapse, and mortality across various age groups of acute myeloid leukaemia (AML) patients. Through a comprehensive search strategy, we identified and synthesized findings from 19 relevant studies.

The results of this review underscore the multifaceted factors influencing the prognosis of patients following either allogeneic or autologous HSCT. Each study highlighted distinct variables that significantly affected overall survival (OS), relapse-free survival (RFS), and transplant-related mortality (TRM), with some factors demonstrating varying impacts across different age demographics.

4.1Overall Survival

Observational studies have identified several determinants of OS in AML patients post-HSCT. Notably, the presence of abnormalities in the 17p chromosome correlated with poorer outcomes across various cytogenetic risk groups. Specifically, patients within the poor cytogenetic risk group showed a significantly lower five-year OS (p < 0.001) when compared to the ones without such abnormalities [4]. Furthermore, younger patients (aged 50 years or younger) demonstrated a higher OS, with rates ranging from 20–23%, while those over 50 years had an OS of only 10% [5]. Similar findings indicated that patients under 40 years of age tend to experience more favourable prognoses post-HSCT [22].

Weight loss due to pre-transplant chemotherapy was associated with inferior OS (p = 0.02), although age did not significantly influence the extent of weight loss (p = 0.2) [17]. Additionally, the binding strength of mutated NPM1 genes to HLA class I molecules was positively associated with prognosis, as evidenced by improved OS among strong binders (p = 0.028) [19]. A retrospective study found that patients with anti-HLA antibodies had a three-year OS of 34%, compared to 16% for those without [3].

Inferior OS was also noted in patients with a higher Charlson Comorbidity Index (CCI > 3) and those classified within the intermediate and adverse risk groups according to the European Leukemia Net criteria [20, 21]. Moreover, urban populations exhibited better five-year OS rates (54%) than rural populations (48%) following either autologous or allogeneic HSCT [24]. No significant differences were observed in patients with inconclusive cytogenetic analyses.

One predictor of OS was the higher age at the time of receiving allogeneic HSCT, which had a hazard ratio of 1.049 [16]. Among children undergoing autologous HSCT, the use of peripheral blood progenitor cells (PBPCs) and the BAVC preparative regimen significantly improved neutrophil recovery rates and positively impacted OS [6]. A randomized controlled trial indicated that there is no significantly different OS between the autologous and allogeneic HSCT groups in paediatric patients [1]. Clinical trials further suggested that HSCT from matched related or unrelated donors was associated with improved OS compared to other transplantation modalities [2].

4.2 Relapse, Relapse-Free Survival, Disease-Free Survival, and leukaemia-Free Survival

The risk of relapse was notably elevated, and DFS was significantly reduced in patients with abnormalities in the 17p chromosome, particularly within the poor cytogenetic risk group, with p-values less than 0.001 for both outcomes [4]. For patients with unclassified or inconclusive cytogenetic analyses, RFS was recorded at 66 months, compared to 42 months for those with conclusive analyses; however, this difference was not statistically significant (p = 0.53) [16].

A retrospective cohort study revealed that male patients receiving HSCT from female donors exhibited a significantly lower relapse rate of 34.1% compared to other gender combinations (p = 0.044). Additionally, the relapse rate was higher in patients under 50 years of age (p = 0.045) [18]. Patients with strong binding of the mutated NPM1 gene to the HLA class I genotype also faced an increased risk of relapse [19].

LFS was poorer in patients classified within the intermediate and adverse risk groups according to the 2017 ELN criteria [21]. In patients with secondary AML, GRFS was reported at 38.8%, while GRFS was lower in patients aged 37 years or younger (40.8%) compared to those older than 37 years (28.7%) [23]. Significant improvements in the five-year relapse rate and LFS were observed in pediatric populations following autologous HSCT [6]. A randomized controlled trial indicated that the relapse rate was higher in children who underwent autologous HSCT compared to those who received allogeneic HSCT [1]. Additionally, lower levels of angiopoietin-2 were associated with improved DFS following allogeneic HSCT [14].

4.3 Non-Relapse Mortality and Transplant-Related Mortality

In contrast to OS, the number of factors influencing NRM and TRM is relatively limited. Notably, the presence or absence of mutations in the 17p chromosome did not significantly impact NRM across various cytogenetic risk groups [4]. Furthermore, NRM was lower in patients categorized within the high loss of body weight (LBW) group compared to those in the low LBW group, with a statistically significant p-value of 0.0025 [17].

NRM was found to be higher in males who received HSCT from female donors compared to other gender combinations (p = 0.005) [18]. A retrospective cohort study reported a TRM of 19.7% in a patient population with a median age of 49 years following allogeneic HSCT [23]. In contrast, children receiving preparative regimens such as PBPCs and the BAVC regimen prior to autologous HSCT exhibited a five-year TRM of only 3% [6]. Remarkably, the TRM was recorded at 0% in children who underwent autologous HSCT [1].

Moreover, NRM was observed to be lower in elderly patients undergoing autologous HSCT (18.2%) compared to those receiving allogeneic HSCT (32.2%). However, OS did not show a statistically significant difference between these groups [8].

4.4 Comparison with Other Evidence

In comparing our findings to existing systematic reviews and meta-analyses, several similarities and differences emerge regarding the outcomes of allogeneic versus autologous HSCT in patients with AML.

One prominent similarity is the focus on overall survival (OS) and relapse-free survival (RFS) as critical outcomes. For instance, a meta-analysis by Li et al. (2015) found that allogeneic HSCT significantly improved RFS compared to autologous HSCT in patients with an intermediate-risk group of AML who are in first complete remission (CR1) [25]. This aligns with our finding that younger patients and those with favorable cytogenetic profiles tend to experience better OS post-allogeneic HSCT.

Additionally, both our review and previous studies highlight the importance of cytogenetic risk in determining outcomes. For example, Mori et al. (2017) demonstrated that patients with 17p chromosome abnormalities had significantly lower OS and higher relapse rates [4]. This is consistent with our findings that cytogenetic factors significantly influence outcomes across different age groups.

Moreover, our findings corroborate those of other studies indicating that younger age is associated with improved outcomes. The meta-analysis by Wang et al. (2010) noted that younger patients undergoing autologous HSCT had better disease-free survival (DFS) and lower relapse rates compared to older cohorts [26]. Similarly, our review found that patients under 40 years had a more favorable prognosis post-HSCT.

Despite these similarities, notable differences also emerged. Our review indicates that transplant-related mortality (TRM) is generally higher in allogeneic HSCT, particularly among older patients. In contrast, the meta-analysis by Cho et al. (2021) found that non-relapse mortality (NRM) was significantly lower in autologous HSCT groups compared to allogeneic HSCT groups [8]. This discrepancy may arise from differences in patient populations, treatment regimens, or definitions of TRM across studies.

Furthermore, our review noted that paediatric patients receiving autologous HSCT experienced higher relapse rates compared to those undergoing allogeneic HSCT, a finding echoed by Dvorak et al. (2008) [1]. However, the systematic review by Locatelli et al. (2003) reported that autologous HSCT resulted in favourable long-term outcomes in children, potentially due to variations in treatment protocols or patient characteristics [6].

Another difference lies in the influence of comorbidities. Our review identified that a higher Charlson Comorbidity Index (CCI) adversely affected OS in elderly patients, a factor less emphasized in previous meta-analyses. For instance, Narayan et al. (2023) focused primarily on age and cytogenetic risk without a detailed exploration of comorbidities, suggesting a potential area for further research [20].

Additionally, we found that urban populations had better OS rates compared to rural populations following HSCT, a factor not commonly addressed in other systematic reviews. This highlights the need to consider socioeconomic factors and access to healthcare services in future research.

Finally, our review discusses the impact of specific preparative regimens, such as the usage of the peripheral blood progenitor cells (PBPCs) and the BAVC regimen, which significantly improved outcomes in paediatric patients. This level of detail regarding treatment protocols is less frequently explored in broader meta-analyses, which may aggregate data without delving into specific therapeutic strategies.

While our systematic review aligns with existing literature on several key outcomes, including OS, RFS, and the impact of cytogenetic risk, it also presents unique insights regarding TRM, the influence of comorbidities, and socioeconomic factors. These findings underscore the complexity of HSCT outcomes in AML and highlight the necessity for individualized treatment approaches based on a comprehensive assessment of patient demographics, genetic factors, and treatment regimens. Future research should continue to explore these variables to enhance our understanding of optimal HSCT strategies across diverse patient populations.

4.5 Strengths of the Review

This systematic review is distinguished by its rigorous methodology, which involved an extensive search across five major databases and one clinical trial register to minimize bias and provide a comprehensive overview of HSCT outcomes for patients with AML across various age groups. The review included a total of 19 studies, encompassing 21977 participants, with a diverse age range from 0.5 to 80 years. This broad scope enhances the generalizability of our findings.

Throughout the search process, including study screening, retrieval, and data extraction, strict adherence to PRISMA 2020 guidelines was maintained. The studies included were assessed to be of moderate to high quality, further bolstering the reliability of the conclusions drawn. Key outcomes evaluated included OS, RFS, and transplant-related mortality TRM, allowing for a robust comparison of allogeneic and autologous HSCT across different age demographics.

4.6 Limitations of Included Studies and Review Process

Despite its strengths, this review has notable limitations. The primary limitation arises from the predominance of observational studies, with only one randomized controlled trial and four clinical trials included. This reliance on observational data restricts the ability to establish causal relationships between the interventions and outcomes, emphasizing the need for more randomized studies in future research.

Additionally, several studies had small sample sizes, specifically 32, 63, and 68 participants [1, 16, 15], which may weaken the robustness of the conclusions drawn. Furthermore, the review exclusively included studies published in English, potentially overlooking relevant research published in other languages, thereby limiting the comprehensiveness of our findings.

4.7 Future Research Directions

Future research should prioritize the inclusion of randomized controlled trials and larger sample sizes to strengthen the evidence base regarding HSCT outcomes. Investigating the impact of specific treatment regimens and patient demographics on survival, relapse, and mortality rates is essential. Additionally, exploring the influence of socioeconomic factors and comorbidities on transplantation outcomes could provide valuable insights for tailoring treatment strategies. Expanding the scope of research to include studies published in multiple languages may also enhance the understanding of HSCT practices and outcomes globally.

This systematic review provides a comprehensive evaluation of the comparative effectiveness of allogeneic versus autologous HSCT in patients with AML across various age groups. The findings highlight the significant impact of demographic factors and cytogenetic risk profiles on OS, RFS, and TRM. Younger patients generally exhibited more favourable outcomes, particularly in terms of OS, while older patients faced increased TRM, underscoring the necessity for age-tailored treatment strategies. The review's rigorous methodology, adhering to PRISMA 2020 guidelines and encompassing 21977 participants from 19 studies, enhances the reliability and generalizability of the results.

Despite its strengths, the predominance of observational studies and the inclusion of only one randomized controlled trial limit the ability to draw definitive causal inferences. Future research should prioritize larger, multicentre randomized controlled trials that assess treatment outcomes and explore the influence of socioeconomic factors and comorbidities on HSCT efficacy. Such studies will be essential in refining treatment protocols and optimizing patient outcomes in AML. Ultimately, this review contributes valuable insights into the evolving landscape of HSCT in AML, reinforcing the importance of personalized medicine in improving survival rates and quality of life for affected individuals.

5.ACKNOWLEDGEMENTS:

Not applicable

Author Contribution

Bandi Venkata Varshitha: Made a major contribution to the article- the conception of the work and collection of data for the work, correction, tables, and figures editing, and drafted the manuscript from introduction to conclusion; Pakeeza Tarar: Participates in selecting data, checking for duplicated data, checking for possible errors, and participating in the drafting of method sections and tables; Rafik Maged Naguib Bishara: Contributed to collecting data, double checks for possible errors, and drafting the introduction and method section; Hema Manvi Koneru: Participated in checking for data collection, references, and drafting the result section and discussion; Hooria Sarwar: Contributed to abstract drafting, discussion editing, data collection, and checking for possible errors; Mohit Sinha: Participated in data collection and abstract editing, ensuring all guidelines are met, and drafts limitation sections; Iana Malasevskaia: Participated in generating ideas, providing suggestions, title modification, corrections, revising the manuscript, and drafting the introduction, method, and conclusion.All authors reviewed the manuscript.

Data availability:

Publicly available data

Code availability:

Not applicable

Dvorak CC, Agarwal R, Dahl GV, Gregory JJ, Feusner JH. Hematopoietic stem cell transplant for pediatric acute promyelocytic leukemia. Biol Blood Marrow Transpl. 2008;14(7):824–30. 10.1016/j.bbmt.2008.04.015. PMID: 18541203; PMCID: PMC2796449.
Schlenk RF, Döhner K, Mack S, Stoppel M, Király F, Götze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Döhner H. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol. 2010;28(30):4642–8. Epub 2010 Aug 30. PMID: 20805454.
Detrait M, Dubois V, Sobh M, Morisset S, Tedone N, Labussière H, Michallet M. Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens. Exp Hematol. 2012;40(10):792–9. https://doi.org/10.1016/j.exphem.2012.06.003.
Mori J, Yanada M, Uchida N, Fukuda T, Sakura T, Hidaka M, Yano S. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Abnormalities of the Short Arm of Chromosome 17. Biol Blood Marrow Transplant. 2017;23(8):1377–84. https://doi.org/10.1016/j.bbmt.2017.04.020.
Middeke JM, Fang M, Cornelissen JJ, Mohr B, Appelbaum FR, Stadler M, et al. Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Blood. 2014;123(19):2960–7. https://doi.org/10.1182/blood-2013-12-544957.
Locatelli F, Labopin M, Ortega J, Meloni G, Dini G, Messina C, et al. Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission. Blood. 2003;101(4):1611–9.
Sengsayadeth S, Labopin M, Boumendil A, Finke J, Ganser A, Stelljes M, et al. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study. Biol Blood Marrow Transpl. 2018;24(7):1406–14. https://doi.org/10.1016/j.bbmt.2018.04.008.
Cho BS, Yahng SA, Min GJ, Park S, Park SS, Shin SH, Kim HJ. Comparable Outcomes After Alternative and Matched Sibling Donor Hematopoietic Stem Cell Transplantation and the Role of Molecular Measurable Residual Disease for Acute Myeloid Leukemia in Elderly Patients. Transplantation Cell Therapy. 2021;27(9):774. 10.1016/j.jtct.2021.05.024.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. 10.1136/bmj.n71.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:210. 10.1186/s13643-016-0384-4.
Wells GA, Shea B, O'Connell D et al. Ottawa Hospital Research Institute: the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. (2021). Accessed: Month, day, 2024: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
Sterne JAC, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hróbjartsson A, Kirkham J, Jüni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schünemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JPT. ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions. BMJ. 2016; 355; i4919; 10.1136/bmj.i4919
Sterne JAC, SavoviÄ‡ J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al. RoB 2: a revised tool for assessing risk of bias in randomised trials BMJ 2019; 366:l4898 10.1136/bmj.l4898
Kümpers P, Koenecke C, Hecker H, Hellpap J, Horn R, Verhagen W, Buchholz S, Hertenstein B, Krauter J, Eder M, David S, Göhring G, Haller H, Ganser A. Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies. Transplantation. 2008;112(5):2139–48. https://doi.org/10.1182/blood-2007-12-130021.
Chang TY, Wang YL, Chang CC, Chen SH, Wen YC, Tsay PK, Jaing TH. Comparable Outcomes Between Adolescent/Young Adults and Children With Acute Myeloid Leukemia Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience. Transplantation Proceedings. 2021;53(10):3075-9. 10.1016/j.transproceed.2021.09.022
Nampoothiri, R. V., Law, A. D., Lam, W., Chen, C., Al-Shaibani, Z., Loach, D., … Viswabandya,A. (2021). Predictors of outcomes of therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Hematology/Oncology and Stem Cell Therapy. https://doi.org/10.1016/j.hemonc.2021.03.003.
Tamaki, M., Nakasone, H., Nakamura, Y., Kawamura, M., Kawamura, S., Takeshita, J.,… Kanda, Y. (2021). Body Weight Loss Before Allogeneic Hematopoietic Stem Cell Transplantation Predicts Survival Outcomes in Acute Leukemia Patients. Transplantation and Cellular Therapy, 27(4), 340.e1-340.e6. https://doi.org/10.1016/j.jtct.2021.01.006.
Kongtim P, Di Stasi A, Rondon G, Chen J, Adekola K, Popat U, Oran B, Kebriaei P, Andersson BS, Champlin RE, Ciurea SO. Can a Female Donor for a Male Recipient Decrease the Relapse Rate for Patients with Acute Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation? Biol Blood Marrow Transpl. 2015;21(4):713–9. https://doi.org/10.1016/j.bbmt.2014.12.018.
Chien SH, Yao M, Li CC, Chang PY, Yu MS, Huang CE, Tan TD, Lin CH, Yeh SP, Li SS, Wang PN, Liu YC, Gau JP. Charlson comorbidity index predicts outcomes of elderly after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. J Formos Med Assoc. 2021;120(12):2144–52. Epub 2021 Jan 8. PMID: 33431375.
Narayan R, Niroula A, Wang T, Kuxhausen M, He M, Meyer E, Chen YB, Bhatt VR, Beitinjaneh A, Nishihori T, Sharma A, Brown VI, Kamoun M, Diaz MA, Abid MB, Askar M, Kanakry CG, Gragert L, Bolon YT, Marsh SGE, Lee SJ. HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia. Transpl Cell Ther. 2023;29(7):452. https://doi.org/10.1016/j.jtct.2023.03.027.
Hansen DK, Kim J, Thompson Z, Hussaini M, Nishihori T, Ahmad A, et al. ELN 2017 Genetic Risk Stratification Predicts Survival of Acute Myeloid Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. Transpl Cell Ther. 2021;27(3):256. https://doi.org/10.1016/j.jtct.2020.12.021. .e1-256.e7.
Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Ritz J, et al. A Prognostic Score for Patients with Acute Leukemia or Myelodysplastic Syndromes Undergoing Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transpl. 2008;14(1):28–35. https://doi.org/10.1016/j.bbmt.2007.07.016.
Park SS, Jeon YW, Min GJ, Park S, Yahng SA, Yoon JH, et al. Graft-versus-Host Disease–Free, Relapse-Free Survival after Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome. Biol Blood Marrow Transpl. 2019;25(1):63–72. https://doi.org/10.1016/j.bbmt.2018.08.004.
Rao K, Darrington DL, Schumacher JJ, Devetten M, Vose JM, Loberiza FR Jr. Disparity in survival outcome after hematopoietic stem cell transplantation for hematologic malignancies according to area of primary residence. Biol Blood Marrow Transplant. 2007;13(12):1508–14. 10.1016/j.bbmt.2007.09.006.
Li D, Wang L, Zhu H, Dou L, Liu D, Fu L, Ma C, Ma X, Yao Y, Zhou L, Wang Q, Wang L, Zhao Y, Jing Y, Wang L, Li Y, Yu L. Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate-Risk Acute Myeloid Leukemia Adult Patients in First Complete Remission: A Meta-Analysis of Prospective Studies. PLoS ONE. 2015;10(7):e0132620. 10.1371/journal.pone.0132620. PMID: 26197471; PMCID: PMC4510363.
Wang J, Ouyang J, Zhou R, Chen B, Yang Y. Autologous hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission: a meta-analysis of randomized trials. Acta Haematol. 2010;124(2):61–71. Epub 2010 Jul 10. PMID: 20616541.
Zhijuan Pan X, Yuan Y, Li X, Wu W, Zhu X, Bao Q, Zhao. Jun He.Dynamic Detection of Anti–Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12–Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies, Biology of Blood and Marrow Transplantation, 22, Issue 1, 2016,Pages 86–95,ISSN 1083–8791,https://doi.org/10.1016/j.bbmt.2015.08.015

No competing interests reported.

Download PDF

Editorial decision: Revision requested
07 Oct, 2024
Reviews received at journal
03 Oct, 2024
Reviewers agreed at journal
02 Oct, 2024
Reviewers agreed at journal
30 Sep, 2024
Reviews received at journal
13 Sep, 2024
Reviewers agreed at journal
03 Sep, 2024
Reviewers invited by journal
03 Sep, 2024
Editor assigned by journal
03 Sep, 2024
Submission checks completed at journal
29 Aug, 2024
First submitted to journal
23 Aug, 2024

You are reading this latest preprint version

Comparing Allogeneic vs. Autologous Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia - Evaluating Outcomes Across Age Groups: A Systematic Review

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

1. INTRODUCTION

2. METHODS

2.1 Search Strategy

2.2 Screening and Quality Assessment:

2.3 Data synthesis

3. RESULTS

3.1 Risk of Bias Assessment

3.2 Characteristics of Included Studies

4. DISCUSSION

4.1Overall Survival

4.2 Relapse, Relapse-Free Survival, Disease-Free Survival, and leukaemia-Free Survival

4.3 Non-Relapse Mortality and Transplant-Related Mortality

4.4 Comparison with Other Evidence

4.5 Strengths of the Review

4.6 Limitations of Included Studies and Review Process

4.7 Future Research Directions

Declarations

5.ACKNOWLEDGEMENTS:

Author Contribution

Data availability:

Code availability:

References

Additional Declarations

Status:

Version 1