Abstract Acute graft vs host disease (aGVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients1. Its pathogenesis involves tissue damage, donor T-cell activation against host antigens, and subsequent organ damage via cytokines and cytotoxicity2. T-lymphocytes have been posited responsible with CD8+ figuring as effectors and regulatory T-cells mitigating severity3. The role of B-cells is not fully understood, with evidence suggesting involvement in antigen presentation or mediation4. Studies show conflicting correlations between graft cell content and aGVHD development. Grafts derived from peripheral blood (PB) pose a higher risk for aGVHD, attributed to a higher T-cell count5, while bone marrow (BM) grafts have a lower risk, but are more susceptible to graft failure and delayed engraftment6. The use of a combination of PB+BM or cord blood has been described as an attempt to reduce aGVHD and transplant related mortality7. This study aims to describe graft composition according to cell source and its impact in the occurrence and severity of aGVHD. Prospective, single center, cohort that included patients ≥18 years undergoing allo-HSCT. Analyzed variables included patient/donor clinical and demographic characteristics, aGVHD severity, overall survival (OS) and disease free survival (DFS). Flow cytometry (BD FACSCanto II) was used to determine graft composition; lymphocytes were identified as T (CD3+) or B (CD19+) and quantified in the allograft. GVHD severity was characterized with the Gluckberg scale. Correlations between CD34+ doses and CD3+/CD19+ in the allograft were analyzed using Spearman's correlations. Associations between cell content and aGVHD severity were compared using chi-squared. The study was approved by the institutional review board. A total of 29 patients were included with a median age of 31 years (18-46), 62.1% were male. Acute lymphoblastic leukemia was the most frequent diagnosis (41.4%) followed by acute myeloid leukemia (24.1%), myelodisplastic neoplasia (17.2%), and aplastic anemia (3.4%); others constituted 13.8%. Myeloablative conditioning was used in 55.2% of patients, reduced intensity in 41.4% and non myeloablative in 3.4%. Donors were haploidentical (69%), match-related (27%), or matched-unrelated (3.4%). Cell source was PB+BM for 17 (58%), and 6 (20.7%) for BM and PB each. Regarding graft composition; medians of infused CD34+ were 2.5×10⁶/kg(2.2-3×10⁶) for BM, 5.1×10⁶/kg(4.9-8×10⁶) for PB, and 5.9×10⁶/kg(2.1-8.7×10⁶) for PB+BM (p=0.031). B cell content was: 113.3×10⁶/kg(84.5-248.9/kg) for PB, 76.1×10⁶/kg(0.9-183.3×10⁶) for PB+MO, and 10.8×10⁶/kg(3.3-16.5×10⁶) for BM(p=0.045). T cells contained were 192.1×10⁶/kg(154-630×10⁶) in PB, 147.13×10⁶/kg(0.3-436.1×10⁶) in mixed source, and 21.4×10⁶/k (12.7-26.4×10⁶) for BM(p=0.241). A positive correlation between CD34+ dose and B-cell allograft content was found (p=0.002). At median follow-up of 8.5 months, OS was 82.7%, and DFS 75.7%. Median time to engraftment 17 days (13-29) with no difference between sources (p=0.82). Rate of aGVHD was 44.8%; 61.5% I-II and 38.5% III-IV. Larger B doses (≥ 84.3×10⁶/kg) were relates with aGVHD(p=0.048), no significant associations existed between stem cell source and aGVHD frequency or severity. No relation was found between donor type and aGVHD. Our analysis describes graft composition according to source, and its impact in the occurrence and severity of aGVHD. Our observed aGVHD rate (44.8%) and time to engraftment (17 days) align with global averages, which range from 30-50% and 13-20 days, respectively8,9. There was no difference between source and aGVHD or time to engraftment, and contrary to classical findings no significant association between CD34+ or T content with aGVHD was found10. Higher B-cells correlated with severity of aGVHD, which aligns with reports suggesting they contribute to the development of aGVHD through inflammatory cytokine production and antigen presentation4. This supports the rationale for using rituximab as a therapeutic agent to prevent or reduce aGVHD severity11. The study's limitations include a lack of detailed lymphocyte subpopulation analysis and the number of patients included. Our findings highlight the complex interplay between graft composition and aGVHD, emphasizing the need for larger prospective studies evaluating the interplay between B and T lymphocytes on acute and chronic GVHD as well as transplant outcomes.
José G. Ávila (Mon,) studied this question.