Favorable impact of pre-transplant ATG on outcomes of reduced-intensity hematopoietic cell transplants from partially mismatched unrelated donors

Abstract

Reduced-intensity conditioning (RIC) permits allogeneic hematopoietic progenitor cell transplantation in patients who would not be considered candidates for transplantation using a myeloablative preparative regimen because of age, comorbidities or prior therapy. In the setting of myeloablative transplantation, use of antithymocyte globulin (ATG) can reduce the risk of GVHD without negatively affecting transplant outcomes; however, limited data exist on the impact of ATG in the setting of RIC, particularly when there is HLA-mismatch. We performed a retrospective analysis of 85 patients who received unrelated donor transplants at our institution for hematologic malignancies following conditioning with fludarabine and melphalan (FluMel), with or without rabbit ATG (6 mg/kg). ATG was targeted to patients receiving HLA-mismatched grafts. With a median follow-up of 36 months, those receiving ATG and a mismatched graft had similar rates of acute and chronic GVHD, relapse, and similar OS compared with those receiving HLA-matched grafts without ATG. In a multivariate analysis, HLA-mismatched donor was not associated with a decrement in OS. We conclude that this intermediate dose of ATG is effective in preventing severe GVHD in the setting of HLA-mismatch, without undue compromise of the graft versus tumor effects on which RIC transplants depend.

Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…In line with previous single-center reports, the negative impact of single mismatch seems to be abrogated by the use of T cell depletion with ATG [41][42][43][44][45]. An important finding from our study is the relative impact of HLA matching and non-HLA donor characteristics on survival after unrelated HSCT.…”

Prospective study of nonmyeloablative, HLA-mismatched unrelated BMT with high-dose posttransplantation cyclophosphamide

“…8,20–22 A report including mMUD BMT described stable engraftment, but also excess GVHD and a 2-year NRM of 47%. 8 Promising results were reported with 1 to 2 locus mismatched mMUD BMT using bortezomib-based GVHD prophylaxis.…”

“…20 Acceptable safety profiles were also reported with mMUD BMT using alemtuzumab 21 and antithymocyte antiglobulin. 22 However, T-cell depletion has been associated with impaired disease-free survival in RIC transplantation 23 and infectious morbidity. 11 …”

Prevention of Prescription Opioid Misuse and Projected Overdose Deaths in the United States

“…1 In October 2017, the US Department of Health and Human Services declared the opioid crisis a national public health emergency. 2 The opioid crisis has also resulted in a substantial cost burden to society—in 2013, health care costs, criminal justice expenses, and productivity losses attributable to opioid misuse were estimated to total $78.5 billion; this cost is expected to increase further in the coming years. 3 …”