In Vivo T-Cell Depletion Does Not Improve Rates of Graft-Versus-Host Disease and Transplantation Outcomes In Patients Undergoing Peripheral Blood Hematopoietic Cell Transplant.

Allogeneic hematopoietic cell transplant (AHCT) is a potentially curative modality for various benign and malignant hematological disorders. Despite advances in supportive care, graft-versus-host disease (GVHD) remains the leading cause of morbidity and mortality following AHCT. In vivo T-cell depletion (TCD) with alemtuzumab or anti-thymocyte globulin (ATG) is commonly employed to prevent graft rejection and GVHD following AHCT. Published (albeit controversial) data suggest possible benefit with TCD in setting of unrelated donor (URD), HLA-mismatched and peripheral blood AHCT. We report here AHCT outcomes for patients who received alemtuzumab or ATG with transplant conditioning (TCD group) and compare them with patients who received T-cell replete allografts (non-TCD group).

The study cohort consists of 150 consecutive patients who underwent AHCT between January 2003 through December 2009. All patients received peripheral blood allografts from matched sibling or URDs. T-cell depletion consisted of alemtuzumab 40mg in two divided doses on days -4 and -1 (n=39) or Thymoglobulin at a total dose of 6 mg/kg for ablative and reduced intensity conditioning (RIC) transplants and 7.5 mg/kg total dose for non myeloablative allografts (n=51). 4 patients received Atgam at 30mg/kg on days -5 to -3.

Of the 150 patients, 62.7% (n=94) were males. Median age was 49yrs (range 17–69). Baseline diagnosis included acute leukemias/myelodysplastic syndrome (n=88; 58.6%), chronic myeloid leukemia (n=19; 12.7%), non-Hodgkin lymphoma (n=27; 18%) and others (10.7%). There were 95 patients (63.3%) in the TCD group and 55 (36.7%) in the non-TCD group. The baseline characteristics of the TCD group and non-TCD group where well matched except for significantly more patients in the TCD group who had high risk disease (86.3% vs. 61.8%, p < 0.05) and received AHCT from URD (62.1% vs. 29.1%, p<0.05). Median follow-up time of surviving patients is 3yrs.

Median time to neutrophil engraftment was 15days (range 7–29 days) overall, with no significant difference between the two groups (p = 0.92). Similarly median time to platelet recovery was 18days (range 4–106), with no significant difference between the two groups (p = 0.85). The incidence of grades II-IV acute GVHD (aGVHD II-IV) in the TCD and non-TCD groups was 42.1% (n=40) and 50.9% (n=28) respectively (p = 0.32). For subgroup of patients undergoing matched sibling AHCT the incidence of aGVHD II-IV in TCD and non-TCD groups was 28.9% (n=11) and 50% (n=18) respectively (p= 0.06). For URD AHCT the corresponding rates of aGVHD II-IV were 48.3% (n=28) and 64.7% (n=11) respectively (p = 0.23). Rates of aGVHD II-IV for patients in TCD and non-TCD group receiving HLA mismatched allografts were also not significantly different (p = 0.59). 110 patients were evaluable for chronic GVHD (cGVHD). The incidence of cGVHD in the TCD and non-TCD groups was 41.1% (n=39) and 45.5% (n=25) respectively (p = 0.86). On subgroup analysis of patients undergoing matched sibling, URD and HLA-mismatched transplants no significant difference in rates of cGVHD between the TCD and non-TCD groups was seen (p>0.05). Relapse rate in the TCD group was 32.6% (n=31) and in the non-TCD group 40% (n=22) (p = 0.22). The overall survival at 3 years was 39.2% in the TCD group and 39.3% in the non-TCD group, (p = 0.93). The 3 year progression free survival in the TCD and non-TCD groups were 34.8% and 27.2% respectively (p=0.85). Non relapse mortality at 100 days similarly were 12.8% and 16% and at 3 years were 40% and 41% in the 2 groups (p>0.05).

Our limited, single institution experience in a cohort of 150 consecutive patients (transplanted within the last decade) suggests no significant benefit with routine use of in vivo TCD with AHCT. These results highlight the need to develop novel and more effective strategies for preventing and treating GVHD and for improving transplantation outcomes.

Abraham:Genentech: Membership on an entity's Board of Directors or advisory committees. Hamadani:Celgene corporation: Honoraria, Speakers Bureau; Otsuka Pharmaceutical: Research Funding, Speakers Bureau.