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INTRODUCTION
Lymphocyte recovery after T cell depleted allogeneic stem cell transplant (allo-HCT) is delayed for at least 6-9 months, particularly after alemtuzumab (AL) administration. Most studies predominantly involving matched sibling donors and T cell replete allo-HCT have shown that early lymphocyte recovery by day 30 is associated with better OS and EFS. Impact of absolute lymphocyte count (ALC) after AL based allo-HCT using unrelated donors (UD) is unknown.
METHODS
We retrospectively evaluated 30 consecutive patients (pts) who underwent allo-HCT from UDs at Markey Cancer Center between January 2010 and May 2012. The primary end point of the study was to evaluate the impact of ALC on transplant outcomes and assess any predictors of higher ALC. Cox proportional hazards model was used for time to event analysis and Odds Ratios were calculated using logistic regression to evaluate for predictors for ALC <= 300 at day 90.AL dose used was 60 mg (20 mg daily x 3 days). Low relapse risk was defined as AML and ALL in CR1, MDS with less than 10% blasts, CLL/NHL/HL with PR and or <5 cm lymphadenopathy and CML in chronic phase.
RESULTS
Median age of the pts was 53.5 yrs (20-67). Patients had AML (12), MDS (4), ALL (5), CLL (4), CML (2) NHL (1), Hodgkins disease (1) and Aplastic Anemia (1). All Pretransplant conditioning included alemtuzumab plus Cyclophosphamide (Cy) TBI for 9 pts, Busulfan (Bu)/Cy for 8 pts and fludarabine (Flu)/Melphalan (Mel) for 13 pts. Seventeen pts had female donors, and 15 pts had donors seropositive for CMV. Source of stem cells was bone marrow (BM) for 16 pts and peripherally mobilized stem cells (PBSCs) for 14 pts. Median CD 34+cells infused were 4.05 x 106 cells/ kg (0.83-12.98). Twenty four pts had high relapse risk.
At day 90 ALC <300 x 106/ml was associated with higher mortality (HR=4.65, p=0.03). In our study, ALC 90 was not associated with GVHD, NRM, CMV reactivation or relapse. ALC 90 >300 x 106/ml was also not associated with donor's sex, CMV status, pt's age, sex, CMV status, CD 34 cells infused ,relapse risk ,HLA mismatch ,source of stem cells or type of conditioning regimen.
After a median follow up of 431 days (118-909), 16 patients are alive. Causes of death were GVHD (6), relapse (2), graft failure (2), infection (2), VOD (1) and hemorrhage (1). Five pts have relapsed. Cumulative incidence of aGVHD (II-IV) was 36.7%, cGVHD (mild, moderate) 13.3%.and CMV reactivation (46.7%).
CONCLUSION
AL is associated with delayed recovery of ALC post allo-HCT. ALC 90 <=300 x 106/ml was associated with four fold higher hazard of death after AL as compared to patients with ALC 90 > 300 x 106/ml at any given time. Further studies are needed to confirm our preliminary findings, to elucidate factors associated with higher ALC90, and ultimately to test proposed interventions to improve ALC90 after allo-HCT.
