Haploidentical transplants for patients with relapse after the first allograft

Abstract

Relapse after allogeneic hematopoietic stem‐cell transplantation (AHSCT) is associated with very poor outcomes. A second transplant offers the possibility of long‐term disease control. We analyzed outcomes with haploidentical donors for second allograft at our institution. All consecutive patients with hematological malignancies (N = 29) who relapsed after AHSCT and underwent a haploidentical transplant (haploSCT) as second transplant between February 2009 and October 2018 were included. Median age was 36 years (interquartile range (IQR) 24‐60); 83% of patients had high/very high disease risk index; 61% of AML/MDS patients had high‐risk cytogenetics; and only 24% were in complete remission at transplant. With a median follow‐up of 46.9 months, the 3‐year relapse, non‐relapse mortality (NRM), progression‐free survival (PFS) and overall survival (OS) were 30%, 39%, 31% and 40%, respectively. In multivariable analysis (MVA), comorbidity index (HCT‐CI) and detectable donor‐specific anti‐HLA antibodies (DSA) prior to second transplant were significantly associated with worse outcomes. Patients with HCT‐CI <3 and without DSA had 3‐year PFS and OS of 53% and 60.3%, respectively. Our findings suggest that haploSCT as second AHSCT is feasible and potentially curative. Lower HCT‐CI and no DSA were associated with lower NRM and improved survival. Haploidentical grafts might be a preferred donor source for second AHSCT as these are high‐risk patients who frequently need to proceed urgently to transplant.

The impact of donor‐specific anti‐human leukocyte antigen antibodies in salvage haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide in patients with nonmalignant disorders

“…In the present study, four out of five patients who failed to engraft died within a median time of 62 days after rescue haplo‐PTCy. The entire cohort's OS at 1 year was 54.5%, which is similar to that reported by other studies with a PTCy platform 14,28 . On the other hand, Fernandes et al 27 reported a higher survival probability, with 10 out of 12 (83.3%) patients alive at a median follow‐up of 45 months.…”

“…The entire cohort's OS at 1 year was 54.5%, which is similar to that reported by other studies with a PTCy platform. 14,28 On the other hand, Fernandes et al 27 reported a higher survival probability, with 10 out of 12 (83.3%) patients alive at a median follow-up of 45 months. In our study, DSA-negative patients had an acceptable 1-year OS of 62.5%, which is consistent with the OS reported for Srour et al 14 Based on our findings and recent recommendations by the European Society for Blood and Marrow Transplantation consensus for donor selection in haplo-HCT, 47 a DSA-negative donor should be chosen for patients with NMDs to avoid a second GF and poor survival after second haplo-HCT.…”

“…Evidence on the role of DSAs after second haplo-PTCy is scarce. 14,15 Although Srour et al showed that DSAs were associated with poor survival outcomes, Giammarco et al failed to confirm the deleterious effects of preexisting DSAs after rescue transplant. However, data on DSA strength and specificity were not detailed in those reports.…”

“…Srour et al described that DSAs were associated with high nonrelapse mortality and poor survival in 29 patients with malignancies who underwent a second haplo-PTCy for relapse. 14 On the other hand, Giammarco et al showed that the presence of DSAs had not affected engraftment in 19 patients receiving salvage haplo-PTCy for primary GF. 15 To our knowledge, the impact of DSAs in salvage haplo-PTCy for rescuing patients with NMDs has not yet been reported.…”

“…Currently, the role of DSAs on salvage haplo‐PTCy outcomes is still debatable. Srour et al described that DSAs were associated with high nonrelapse mortality and poor survival in 29 patients with malignancies who underwent a second haplo‐PTCy for relapse 14 . On the other hand, Giammarco et al showed that the presence of DSAs had not affected engraftment in 19 patients receiving salvage haplo‐PTCy for primary GF 15 .…”