In Vivo T Cell Depletion with Thymoglobulin or Alemtuzumab Is Associated with Worse Outcome Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients Transplanted in Remission

In vivo T Cell Depletion with Thymoglobulin or Alemtuzumab Is Associated With Worse Outcome Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients Transplanted in Remission.

Allogeneic hematopoietic stem cell transplantation (HSCT) reduces relapse risk in adults with acute myeloid leukemia (AML) due in large part to the potent graft-versus-leukemia effect of donor lymphocytes.  However, this benefit must be balanced by the increased morbidity and mortality associated with graft-versus-host disease (GVHD).  Serotherapy, in the form of thymoglobulin or alemtuzumab, has been used for in vivo T cell depletion as a strategy to reduce GVHD.  We analyzed 144 consecutive AML patients transplanted in remission (CR1 – 111, CR≥2 – 33) from either a matched related (MRD, n=44), unrelated (MUD, n=62), or haploidentical (haplo, n=38) marrow of PBSC donor, in order to analyze the effect of serotherapy, in relation to other disease-, patient- and transplant-related risk factors, on post-transplant outcomes.  Patients were transplanted at a single institution between 3/15/06 to 12/19/14.  Baseline characteristics of the patient cohort included age >50 in 88 (61%), KPS<90 in 93 (65%), CMI ≥3 in 61 (42%) of patients.  Disease risk index (DRI) was defined as low, intermediate, and high in 5 (4%), 110 (76%), and 29 (20%) patients respectively per the revised Dana Farber/CIBMTR criteria.  Myeloablative chemotherapy was given in 96 (67%) patients, and PBSC was the source of stem cells in 120 (83%) patients.  Serotherapy was utilized in 21 (15%) patients [thymoglobulin – 8, alemtuzumab – 13].  Serotherapy patients were more likely to be older (median age 59 vs. 52 years, p=0.013) and have a MUD (81% vs. 37%, p<0.001), but otherwise had similar baseline characteristics in regards to disease status, DRI, regimen intensity.  Acute GVHD grade II-IV occurred in 38% of patients, whereas chronic GVHD was seen in 44%.  Chronic GVHD occurred less often in patients receiving serotherapy (19% vs. 49%, p=0.016).  Estimated one year non-relapse mortality (NRM) at 1 and 3 years was 4% and 13% respectively and was statistically similar in serotherapy and non-serotherapy patients.  The estimated 3 year OS, DFS, and relapse was 58%, 51%, and 37% respectively for the whole cohort; 64%, 55%, and 33% in non-serotherapy patients vs. 29%, 27%, and 57% in serotherapy patients (figure 1).  Cox analysis was performed utilizing the following variables: age, disease status, DRI, KPS, CMI, transplant type (MRD, MUD, haplo), conditioning intensity, stem cell source, use of serotherapy, year of transplant, acute and chronic GVHD.  Variables were selected by a 10% threshold.  Acute and chronic GVHD were modeled as time-dependent variables.  In multivariate analysis, unfavorable risk factors for survival included only two variables: the use of serotherapy (HR 3.11, p<0.001) and high risk DRI (HR 1.89, p=0.038).  Use of serotherapy also had a negative effect on relapse (HR 2.69, p=0.003) and DFS (HR 2.73, p<0.001), with no effect on NRM. Following allogeneic HSCT for AML patients in remission, the use of serotherapy for in vivo T cell depletion had a major negative impact on survival due to increased relapse risk.