Peripheral Blood Grafts for T Cell–Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome

Abstract

T cell-replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34 stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade < 2) was not associated with differences in overall survival or nonrelapse mortality. Severe CRS was associated with a statistically nonsignificant trend toward higher incidences of grades III to IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T cell-replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.

Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide

“…Different studies showed similar results. 6,24 In our analysis in the haplo-HSCT cohort a number of TNC infused greater tan 6x10 8 / kg significantly increased the probability of developing CRS. Concomitantly, the fact that CD34+ cells infused did not correlate with the occurrence of CRS, suggests that T-cell content might play a significant role, since it is the largest cell subset in PBSC mobilized with G-CSF from healthy donors.…”

“…12,13 In this retrospective study, we with previous autologous transplantation) and also to a different criteria for CRS grading. 6 In another study with a similar transplant platform, Abboud R. et al analyzed CRS in a total of 75 patients. Nine of them had CRS grades 3 to 4, and seven were treated with tocilizumab.…”

“…Fever usually disappears after administration of PTCy, probably due to the marked depletion of alloreactive infused T-cells. 6 CRS is usually well tolerated and only a small percentage of patients require special measures in intensive care units. Ramzi Abboud et al analyzed 75 patients who underwent haplo-HSCT with PTCy.…”

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide

“…On the other hand, McCurdy et al [38] reported that CRS occurred in 44% after NMA-based PTCy-haploBMT, and 84% after MAC-based PTCy-haploBMT. Raj et al [39] demonstrated that PBSCT was significantly associated with grade ≥ 2 CRS, compared with BMT. With regard to the risk of CRS, McCurdy et al reported that CRS after PTCy-haploBMT is associated with myeloablation, HLA-class II mismatching, and higher CD3 + graft cell dose.…”

Teaming up for CAR-T cell therapy

“…The reason for this is that allotransplant specialists will have the greatest experience in the treatment of the potential severe CAR-T cell-induced side effects. 15,16 In the article by Moreau et al in this edition of Haematologica, European Myeloma Network (EMN) experts discuss the future use of CAR-T cell therapies in multiple myeloma patients (by multiple myeloma experts, rather than an allogeneic team) as highly relevant and warranted. 17 The recommendation for specialist care by allogeneic-transplant specialists in CAR-T-cell therapies is, therefore, debated by Moreau et al for myeloma patients, one reason being that centers with leading expertise in myeloma treatment including autologous stem cell transplantation may not necessarily have a unit for allogeneic transplantation.…”