Hematopoietic Recovery and Transfusion Needs after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Adult Patients with Hematologic Malignancies

Introduction:

Haploidentical stem cell transplantation (Haplo-SCT) using post-transplant cyclophosphamide is widely used for the treatment of patients with hematologic malignancies especially in patients who lack related or unrelated donors. Several factors were shown to affect hematopoietic recovery after allogeneic hematopoietic stem cell transplantation, including age at transplant, initial diagnosis, stem-cell source, CD34 count in the graft, conditioning regimen intensity, infections, etc. The aim of this study was to evaluate immune reconstitution, neutrophils and platelets recovery, transfusion needs and main transplant outcomes after Haplo-SCT and to identify factors correlated with improved or worsened recovery.

Methods:

This study included 72 consecutive patients who underwent haploidentical stem cell transplantation between December 2012 and March 2018, in a single center. Graft was either bone marrow (n=21) or peripheral blood stem cells (n=51). Patients were given PT-Cy (50mg/kg/d) for one (n=20) or two days (n=52), cyclosporine, mycophenolate mofetil and ATG for GvHD prophylaxis. Conditioning regimen was reduced toxicity one (RIC) in 69% (n=50) of patients, and a myeloablative one (MAC) in 31% (n=22) of cases .

Main transplant outcomes, neutrophil and platelets recovery, and needs for transfusion were evaluated at day +30, day +60 and day +90 after Haplo-SCT.

Results:

The median CD34+ cells infused was 10.62 x10⁶/kg (range, 1.02-15.06). The median time to neutrophil recovery (>500/µL) was 16 days post-transplant (range, 5-29). The median time to neutrophil count >1000/µL was 17 days post-transplant (range, 5-32). Platelets recovery (>20.000/µL) was observed at a median of 13 days post-transplant (range, 10-193). Platelets recovery (>50.000/µL) was documented at a median of 60 days post-transplant (range, 10-193). Forty-five (63%) and 49 (68%) patients had a platelets count >50.000/µL at days +30 and +60 post-transplant respectively. At day +90 post-transplant, 61 patients were assessable with 56 (92%) of them having a platelets count >50.000/µL.

In this series, 61 patients (85%) needed platelets transfusion with a median number of 13 units (range, 2-60), transfused for a median of 26 days (range, 5-198) post-transplant. Similarly, 59 patients (82%) needed RBCs transfusion and received a median of 6 RBCs packs (range, 1-60) for a median duration of 31 days (range, 5-147) post-transplant. 23 patients (32%) had anemia and/or thrombocytopenia requiring the administration of growth factors, either erythropoietin in 14 patients (19%) (Epoetin, n=8 or Darbepoetin, n=6) and/or Thrombopoietin in 15 patients (20%) (Romiplostim, n=13 or Eltrombopag, n=2).

In all, 6 patients received unmanipulated CD34+ donor stem cell ("boost" procedure), 5 of them for poor graft function and 1 patient as a consolidation after immunosuppressive therapy for relapse after Haplo-SCT. Such boost proved to be successful in 4 patients while 2patients had an incomplete response with persistent anemia and/or thrombocytopenia.

In the multivariable analysis, donor age (>40 years) and CMV reactivation within the first 3 months were shown to meaningfully affect day +90 platelets recovery >100 x10⁹/L (HR 4.86, 95%CI 1.08-21.80, p=0.04 and HR 5.15, 95% CI, 1.22-21.7, p=0.03). Number of CD34, conditioning regimen, stem cell source, donor age and disease status at transplant have no impact on platelet recovery at day +90.

Conclusion:

In conclusion, our data show that Haplo-SCT is associated with a fast hematopoietic recovery with an acceptable rate of transfusions. While the adverse impact of CMV reactivation on platelet recovery was expected, the relation between donor age (>40 years) and platelets recovery is new. This finding should guide in selection of potential donors for Haplo-SCT.