CD34 Chimerism Directed Donor Lymphocyte Infusion With or Without Azacitidine Results in Reduced Relapse and Superior Overall Survival When Full Donor Chimerism is Achieved in Allogeneic Stem Cell Transplant Recipients With Acute Myeloid Leukaemia/Myelodysplastic Syndrome.

BACKGROUND: Regular monitoring of CD34 donor chimerism (DC) is a highly sensitive method of predicting relapse in allogeneic stem cell transplant (alloHSCT) recipients with AML/MDS. A fall of CD34 DC below 80% is an indicator of ensuing relapse. There are limited studies assessing the efficacy of donor lymphocyte infusion (DLI) triggered by mixed CD34 DC (MDC), in addressing falling chimerism. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive alloHSCT patients between 2012 to 2023 who received DLI (with or without azacitidine) for CD34 MDC without morphologic relapse at the time of infusion. RESULTS: Of the 21 patients with follow up CD34 DC available, 14 (66.7%) achieved CD34 full donor chimerism (FDC) following DLI with or without azacitidine (dli-FDC), while 7 (33.3%) did not (dli-MDC). The 2-year cumulative incidence of relapse (CIR) was significantly lower in dli-FDC compared to dli-MDC (21.4% vs. 85.7%, P < 0.001), correlating with superior overall survival (OS; median years not reached vs. 0.67 years [95% CI, 0.58-ND], P < .001). Rates of grade II-IV acute GVHD post-DLI were 14.9%, and moderate-severe cGVHD was 42.8% in the dli-FDC group. The 5-year nonrelapse mortality (NRM) of the dli-FDC group was 7.1% following DLI. CONCLUSION: Our study shows the restoration of CD34 FDC post-DLI is associated with reduced relapse and improved overall survival, with low NRM.

Cardiovascular and Metabolic Risk Incidence Among Adult Allogeneic Stem Cell Transplant Recipients: A Narrative Review.

Advances in allogeneic hematopoietic stem cell transplantation (alloHSCT) and supportive care over the past decade have reduced transplant and relapse-related mortality, leading to a greater number of long-term survivors. However, transplant-related late effects, such as cardiovascular disease (CVD) and metabolic diseases, are becoming significant concerns for this group. This review aims to address several key questions regarding cardiovascular late effects in alloHSCT recipients, including the long-term incidence of CVD-related events, the prevalence of risk factors, screening and management recommendations, and evidence for screening and prevention strategies. A literature search was conducted in PubMed Central using the National Library of Medicine search engine, covering all relevant research from inception to 2023. The initial search identified 751 research records, of which 41 were shortlisted based on specific criteria (≥18 years of age at the time of transplant, allogeneic transplant, and inclusion of more than 30 patients). Our review highlights published evidence confirming the increased CVD risk among alloHSCT recipients. This risk is especially pronounced among individuals who have developed traditional and modifiable risk factors or have been exposed to transplant-specific risk factors. Evidence of the use of traditional cardiac risk factor calculators in the alloHSCT population is limited, in addition, there is emerging evidence that general population calculators potentially underestimate CVD risk given the increased risk of CVD in the allogeneic group as a whole. Studies that develop and validate transplant recipient-specific CVD risk stratification tools appear to be severely lacking and the field's focus needs to be shifted here in the coming years. To improve patient engagement and adherence to CVD risk factor measures, we recommend that a multidisciplinary model involving both specialists and primary care physicians is crucial in ensuring regular follow-up in the community and to potentially improve adherence.

Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC) monitoring.

INTRODUCTION: This longitudinal study was based on the outcomes of Donor Lymphocyte Infusion (DLI) for falling peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC). METHODS: From 2012 to 2018, data was collected from the BMT database and electronic medical records (EMR). The primary objective was to compare the indication for DLI based on falling PB CD34+ or CD3+ DC in patients post allo-SCT for AML and MDS and their overall survival (OS). RESULTS: 18/70 patients met the inclusion criteria. Indications for DLI were i) falling PB CD34+ DC ≤ 80 % with morphological relapse, ii) falling PB CD34+ DC ≤ 80 % without morphological relapse and iii) falling PB CD3+ DC ≤ 80 % without falling PB CD34+ DC. Log rank analysis showed falling PB CD34+ DC and morphological relapse had significantly lower OS. Linear regression demonstrated better OS post DLI if there was PB CD34+ and CD3+ chimerism response at 30 days (p = 0.029), GVHD (p = 0.032) and tapering immunosuppression at the time of falling DC (p = 0.042). CONCLUSION: DLI for PB CD34+ DC values ≤ 80 % and morphological relapse had the lowest OS. In this study, full DC was achieved after DLI even with a PB CD3+DC value as low as 13 %, provided the PB CD34+ DC remained > 80 %. Further research is vital in CD34+ DC as a biomarker for disease relapse and loss of engraftment.