High Relapse Rate Following Alemtuzamab Use in Allogeneic Transplants for Myeloid Hematologic Malignancies.

Chakravarti, (Blood, 2002, p1071) and others have described the use of alemtuzamab, a monoclonal antibody that binds to CD52 on T cells, B cells, monocytes and dendritic cells in vivo for control of graft vs host disease in reduced intensity or fully-ablative matched related and unrelated transplant regimens for hematologic malignancies. Control of GVHD has been good, but high relapse rates and infectious complications have been seen. We report our experience with 42 pts who underwent matched related (27) or unrelated (15) bone marrow (8), blood stem cell (33), or both (1) transplants for hematologic malignancies. There were 16 women and 26 men, median age 48, and median f/u is 9 months. All AML pts had high-risk disease defined as beyond CR1 (11), CR1 with high risk cytogenetics (5), AML with tri-lineage dysplasia (6), or failed prior autologous transplant (1) Three had >10% marrow blasts at time of transplant. All other pts had advanced and multiply recurrent disease. All pts received alemtuzamab either at 20 mg/m2/d x 5 (17), or 30 mg/m2/d x 3 (25) between days -8 through -4. The conditioning regimens also included 12.8 mg/kg IV busulfan, (27), 6.4 mg/kg IV busulfan (8), melphalan 140 mg/m2 (6), or Cy/TBI (1). All non-TBI patients received 30 mg/m2/d x 5 of fludaribine. Median recovery of ANC to >500/ul and platelets > 20,000/ul w/o transfusion were 13 and 14 days, respectively. TRM included 1 pt each with intracranial hemorrhage at day 8, multi-organ failure/sepsis at day 28, and IPS/ARDS at day 119. Two of the 3 deaths were in MRD transplants; no serious episodes of VOD were observed. Grade 2–4 GVHD was seen in 4/14 evaluable MUD pts and 1 (sex mismatched) of 26 evaluable MRD pts. CMV reactivation has been seen in nearly all CMV sero+ pts, and bk reactivation was seen in 25 pts with hemorrhagic cystitis in 10. One case of PTLD, 3 graft failures, and one severe case of disseminated adenovirus infection resulting in nephritis, cystitis and transient cardiomyopathy were also seen. Relapse/# evaluable for different diseases are as follows: AML 12/22, Gleevec-resistant CML 3/3, MDS 0/4, MM 3/3, NHL 0/3, ALL 0/3, CLL 0/2. Relapse rates in evaluable MRD pts, 15/26 (58%), were statistically higher compared to MUD pts, 3/14 (21%) (p = 0.05). RR in marrow, 2/8, vs BSC, 16/32, were comparable. Alemtuzamab use has been effective at controlling GVHD and infectious complications can be reduced with early and pre-emptive use of ganciclovir. Nevertheless, high relapse rates remain a significant problem and preclude routine use of this approach in MRD patients with advanced myeloid diseases. Current use of this agent has been individualized for donor (MRD vs MUD) and disease (myeloid vs other) status.〉