Prospective Study of Allogeneic Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide and Antithymocyte Globulin from HLA-Mismatched Related Donors for Nonmalignant Diseases

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is performed as a curative treatment for children with nonmalignant diseases, such as bone marrow failure syndromes and primary immunodeficiencies. Because graft-versus-host-disease (GVHD) is a major factor affecting survival probability and quality of life after HSCT, the availability of HLA-matched donors restricts the application of HSCT. Recently, HSCT with post-transplantation cyclophosphamide (PTCy) has emerged as a potent method to prevent GVHD after HSCT from HLA-haploidentical donors, and some studies have suggested the safety of PTCy-HSCT for nonmalignant diseases. We conducted a prospective clinical trial aiming to help confirm the safety of HSCT and further reduction of GVHD using a combination of PTCy and low-dose antithymocyte globulin (ATG) from HLA-mismatched related donors for children with nonmalignant diseases. Six patients underwent HSCT and achieved engraftment at a median of 14.5 days, and no patient developed severe acute GVHD. All patients had sustained donor chimerism without developing chronic GVHD at the last follow-up. In conclusion, HSCT with PTCy and low-dose ATG from an HLA-mismatched related donor were feasible to control GVHD for nonmalignant diseases in the children involved in our study.

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985–2016

“…For patients who received HCT from ORD, we observed a poor OS/EFS, as well as poor engraftment and a high incidence of cGVHD. In our cohort, post-transplant cyclophosphamide or TCRαβ + /CD19 + depletion, which are beginning to be adopted in haploidentical HCTs for IEIs worldwide [21][22][23][24][25][26] as well as in Japan [27],…”

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other Than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985–2016

“…For patients who received HCT from ORD, we observed a poor OS/EFS, as well as poor engraftment and a high incidence of cGVHD. In our cohort, post-transplant cyclophosphamide or TCRαβ + /CD19 + depletion, which are beginning to be adopted in haploidentical HCTs for IEIs worldwide [21][22][23][24][25][26] as well as in Japan [27], was not used in most of the cases. The introduction of these novel techniques can expectedly help exploit more available donors and also improve the outcome of HCT from ORD in the coming decades.…”

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Anti-Thymocyte Globulin (ATG) Administration Schedules in Allogeneic Stem Cell Transplantation

“…Administration of ATG on a different schedule than the conventional time window of pre-graft infusion is one way to allow adequate immune reconstitution without adversely impacting chronic GVHD risk, and allow dose de-escalation of PT-CY. Indeed, rabbit ATG 2.5 mg/kg given on day -8 thru -5 when added to PT-CY leads to reliable engraftment with no GVHD risk 30 . Similarly, the ATG schedule reported here leads to improved ETIR without a noticeable impact on overall GVHD risk and with a trend towards improved survival and relapse in the two patient groups studied.…”

“…Cut offs for the angle of the vector were established in the same manner, and were 35°, 50°, and 55° for day 30, 60, and 90 respectively. There was a significant difference with an angle >34.65° on day 30 9). These were all associated with greater NRM in these individuals (univariate HR 10, p=0.008; multivariate HR 12, p=0.019).…”