Abstract
T-cell replete Haplo-SCT using PT-Cy as GVHD part of prophylaxis has become a valid option to perform allogeneic transplantation in patients without an available HLA-matched donor. The absence of additional ex vivo procedure has participated to its increasing use in the field of transplantation. Because of HLA disparity, bone marrow (BM) was initially chosen as stem cell source, based on previous observations of lower incidences of GVHD after HLA-matched donor transplantation, when using BM graft as compared with G-CSF mobilized peripheral blood stem cells (PBSC). In contrast, use of PBSC may improve engraftment and disease control favoring larger adoption of the procedure. However, the use of PBSC graft for Haplo-SCT remains controversial. We here report our experience of PBSC Haplo-SCT using PT-Cy for hematological malignancies.
We selected patients (pts) with hematological malignancies who underwent Haplo-SCT using PT-Cy at 2 transplant centers from March 2012 to June 2016, using the following criteria: PBSC as graft source; first allogeneic transplantation; PT-Cy as part of GVHD prophylaxis. Patients with refractory acute leukemia who received sequential conditioning regimens were excluded. GVHD prophylaxis included PT-Cy (D+3 and D+4) in association with calcineurin inhibitors and MMF started from D+5.
The aim of this retrospective study was to provide a comprehensive description of GVHD following PBSC Haplo-SCT with PT-Cy. Beyond calculation of the cumulative incidence of both acute and chronic GVHD, we precisely describe GVHD features by grading organ involvement and severity. In addition, we assess the prevalence of GVHD and immunosuppressive treatment (IST) at 3, 6, 9, 12, 15, 18, 21 and 24 months after Haplo-SCT in disease free patients, as well as quality of life.
We retrospectively analyzed 181 consecutive pts with a median age of 60 years (19-73). Ninety-seven (54%) pts were affected by myeloid diseases, mostly (29%) AML. Disease risk index was high or very high in 47 pts (26%). Non-myeloablative conditioning regimen (low dose TBI + cyclophosphamide and fludarabine) was used in 92 pts (51%), while the remaining patiens received busulfan-based conditioning regimen, with reduced and myeloablative doses in 67 pts (38%) and 21 (12%) pts, respectively.
The median CD34+ and CD3+ cells infused were 5.3 x 10^6/kg (range, 1.5-18.1) and 280 (range, 38-704), respectively.
Median time to neutrophil recovery (ANC >500 x106/L) was 21 days (range, 17-112) and 30 days (range, 10-394) to platelet recovery (PLT > 20 G x 109/L).
Between 24-48 hours after donor stem cells infusion, 88% of recipients experienced fever with chills (median temperature = 40,1°C). No microbiological proof of infection was found in most pts, while bacterial infection was identified in bloodstream culture in 9 % of pts.
Fever completely disappeared the day after the last PT-Cy infused dose in 79% of patients.
The incidence of grade II-IV and III-IV aGVHD was 23% and 8% at 100 days, respectively. Among patiens who developed aGVHD, 58 (82%) presented with isolated skin involvement, while gut GVHD was responsible for most grade III-IV GVHD (16/20, 80%).
The cumulative incidence of cGVHD was 18% at 2 years. According to NIH classification, half of the patients who developed cGVHD presented with mild forms, without needing systemic treatment (mostly skin and mucosa involvement), while severe forms occurred in 3% of GVHD cases.
As shown in Figure 1, at 6 months post Haplo-SCT, IST was discontinued in 40% of disease-free patients. In addition, most patients who were disease-free at 2 years were living with no immunosuppressive treatment (98%) and no GVHD (94%).
At 2 years, NRM, relapse, PFS, OS and GRFS were 21%, 17%, 62%, 66% and 50%, respectively
We conclude that PBSC Haplo-SCT using PT-Cy is a feasible procedure, with low incidences of severe forms of both acute and chronic GVHD. In addition, we pointed out that almost all surviving patients were living without GVHD and IST at 2 years, suggesting a preserved quality of life. Thus, as previously shown using BM as graft source, PT-Cy allows performing T-replete Haplo-SCT with low incidence of GVHD also using PBSC, with very low long term GVHD-related morbidity.
No relevant conflicts of interest to declare.
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