PF759 ALLOGENEIC STEM CELL TRANSPLANTATION FOR HEMATOLOGICAL MALIGNANCIES FROM HLA IDENTICAL SIBLINGS OR HAPLOIDENTICAL DONORS: A COMPARISON
Authors: Corbingi A. , Dragonetti G. , Galli E. , Raiola A.M. , Dominietto A. , Di Grazia C. , Van Lint M.T. , Chiusolo P. , Sorà F. , Giammarco S. , Sica S. , Laurenti L. , Bacigalupo A. 
Published: June 2019

Background:

Allogeneic stem cell transplantation (HSCT) from an HLA identical sibling donor(SIB) remains standard of care. When a SIB donor is lacking, HLA mismatched related donors (HAPLO) are a valid alternative source of stem cells. The outcome of SIB and HAPLO transplant have been evaluated and often found to be comparable.

Aims:

The aim of the present study is to compare the outcome of patients allografted from HAPLO or SIB donors in two transplant Units between 2010 and 2017, in terms of engraftment, GvHD, non relapase mortality (NRM), relapse and survival.

Methods:

678 patients were eligible for this study: 195 patients (29%) grafted from SIB donors and 483 (71%) from HAPLO donors. The main diagnosis were acute leukemias (55%) and myelodysplastic syndromes (20%), followed by lymphomas and myelofibrosis. The two groups were comparable in terms of recipients age (p = 0.3), donors age (p = 0.8) and status of disease at the time of HSCT; 401 patients were in CR1–2 (123 vs 288, p = 0.4) and 266 patients were beyond CR2 (72 vs 194). The stem cell source was bone marrow for all patients grafted from HAPLO donors; it was peripheral blood in 43% SIB grafts and 47% in bone marrow grafts. The conditioning regimen was full dose total body irradiation in 27% and 16% (SIB vs HAPLO), thiotepa, busulfan, fludarabine, in 69% vs 72% and a non myeloablative regimen in 3% vs 11% (p < 0.001).

GvHD prophylaxis was cyclosporin (CyA) and methotrexate (MTX) for SIB grafts and CyA+ mycophenolate (MMF)+ post transplant cyclophosphamide (PT‐CY) for HAPLO grafts.

Results:

Neutrophils engraftment was achieved in SIB vs HAPLO grafts at a median day of 17 (10–71) and 18 (13–64) days respectively (p = 0.6). Platelet recovery was faster after SIB grafts with platelet counts of 132x10^9/L vs 88 x10^9/L on day +50 after HSCT (p < 0.00001). The cumulative incidence of acute GVHD grade 3–4 and chronic GVHD moderate to severe was higher in SIB vs HAPLO grafts: respectively 9% vs 3% (p = 0.001) and 32% vs 21% (p = 0.002). Platelet counts were significantly higher on day +50 in SIB vs HAPLO grafts, when stratified for acute GvHD grade 0‐I (141x10^9/L vs 95 x10^9/L) or acute GvHD grade II (104x10^9/L vs 57x10^9/L; p = 0.008). We found no difference in terms of transplant‐related mortality (TRM) (17% vs 19%, p = 0.5), 5 years survival (55% vs 54% p = 0.4) and relapse (32% vs 28%, p = 0.4).

In a multivariate Cox analysis predictors of survival were advanced disease (RR 1.9, p < 0.00001), recipients age > 40 years (RR 1.4, p = 0.03) and over 60 years (RR 1.8, p = 0.003). The only predictor of NRM was patients age, and the only predictor of relapse was advanced disease.

Summary/Conclusion:

This study suggests that major transplant outcomes, are comparable in SIB vs HAPLO grafts, namely mortality, relapse and survival. GvHD is somewhat greater in SIB patients, but GvHD prophylaxis is less intense. Hematologic recovery is faster and more robust in patients receiving SIB transplants, also after stratifying for GvHD. HAPLO grafts remain a valid alternative source of stem cells in the absence of an HLA identical SIB.

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