Gemtuzumab Ozogamicin Combined with Hyper-CVAD in Relapsed Refractory CD33-Positive Acute Lymphoblastic Leukemia.

Adult patients with relapsed or refractory ALL have a dismal clinical prognosis. The CD33 antigen is expressed on leukemic cells of approx 30% of all ALL cases. For such patients, a combination of an anti-CD33 MoAb with chemotherapy may provide an effective therapeutic option, although clinical data are yet scarce. Here we describe our experience using gemtuzumab ozogamicin (Mylotarg), an anti-CD33 antibody linked to calicheamycin, combined with cytostatics as reinduction chemotherapy for two relapsed, refractory CD33-pos ALL patients.

Case 1. A male 32 yr old patient diagnosed with pre-B-ALL in April 2004. He showed no poor-risk criteria at diagnosis but needed two induction courses to enter complete remission (CR). After having received two cycles of consolidation therapy and a maintenance treatment he relapsed in October 2004. He then failed to respond to reinduction chemotherapy with RIEHM AA (Holoxan, Oncovin, Emthexat, Betamethason, Cytarabine, Etoposid) and MEA-Asp (Novantrone, Cytarabine, Etoposid, Asparaginase). As a 3^rd reinduction option he was given “hyper-CVAD” (Cyklofosfamid, Oncovin, Doxorubicin, Dexamethason) combined with Mylotarg (6mg/sqm on day 10). The patient then achieved a full CR on day 28 and was scheduled for a subsequent allogeneic transplantation with an unrelated donor. However, due to an extended toxic colitis he was unable to receive consolidation treatment and again relapsed on day 36 after CR. Shortly thereafter the patient died in a septic shock.

Case 2. A 19 yr old female patient was diagnosed with pre-B-ALL without poor-risk criteria in November 2001. After standard induction therapy she achieved CR and received maintenance treatment until May 2002. In May 2003 bone marrow relapse occurred, but she entered a 2^nd CR after reinduction chemotherapy and successfully underwent an allogeneic stem cell transplantation from a matched unrelated donor in September 2003. A second relapse occurred in January 2004. The patient then received reinduction with hyper-CVAD combined with Mylotarg, as described above. This resulted in a 3^rd CR. Subsequently she received an identical consolidation course followed by DLI in March 2004. She remained in CR until February 2005 when she again relapsed and died in respiratory insufficiency.

Conclusion. The combination of gemtuzumab ozagamicin and hyper-CVAD may provide a logical, feasible and possibly effective therapeutic option for relapsed and refractory CD33-pos ALL patients.