Efficacy and Safety of Gemtuzumab-Based Regimens in Patients with CD33-Positive Refractory Leukemia.

Patients with relapsed or refractory leukemia have less chances of obtaining remission than patients with newly diagnosed.It is reported that more than 80% of acute myeloid leukemia(AML) patients have myeloid blast cells that express the CD33 surface antigen. This antigen also is present on the leukemic stem cells at least some patients with chronic myeloid leukemia(CML)and acute lymphoblastic leukemia(ALL). It is absent from normal hematopoietic stem cells and nonhematopoietic cells and tissues. Gemtuzumab is a humanized anti-CD33 antibody conjugated to calicheamicin, a potent anti tumor antibiotic derived from a bacterium. It is conditionally approved in the US for treatment of CD33+ AML in first relapse in patients over 60 years[Sievers et al.Journal of Clinical Oncology,2001]. Here we evaluate the efficacy and safety of Gemtuzumab -based regimens. The study population comprise 11 patients with CD33-positive refractory leukemia (determined as CD33-antigen expression in over 50% of leukemic blasts by bone marrow aspirates and immunophenotyping), including two with myeloid blast phase of CML, one with refractory ALL, two relapsed after Auto-stem cell transplantation(Auto-SCT). The median age was 47 years. Four cases who were over 60 years or after Auto-SCT treated with single agent. The other seven cases treated with mylotarg and cytotoxic agents, including mylotarg plus idarubine (MI); Gemtuzumab plus fludarabine, cytarabine, CsA(MFAC); or plus mitoxantrone, Ara-C (MMA).The overall response rate was 54% (6/11), with 36%(4/11) patients obtaining complete remission (CR) and 18% (2/11) achieving CRp.The median overall survival time after treatment was 4.8 months, and the median overall survival time after CR was 8.2 months.Two patients with myeloid blast phase of CML achieved CR with BCR/ABL(−), the survival time after CR was 5+months and 20+months respectively, but failed in second relapse. One patient received Allo-SCT after CR with refractory ALL is still alive at present (21months) with disease free. The median time to ANC recovery of 0.5×10⁹/L was 15 days.The common adverse events was myelosuppression (100% Grade 4 neutropenia and thrombocytopenia).Significant non-hematologic toxicitics included infection(96%), infusion-related chills and fever (55%).Although hepatic dysfunction and mucositis were observed,they were generally infrequent and not severe(Grade 1–2).Six patients (55%) developed Hepatic veno-occlusive disease(VOD), four of them were either over 60 years old or received Auto-SCT before although they received only single agent mylotarg therapy, but it was transient and no one died from it. In conclusion, patients with CD33-positive refractory leukemia, Gemtuzumab -based regimens have a comparable response rate and offer a more favorable toxicity profile, expecially for the patients with myeloid blast phase of CML. It is also effective for the patient with refractory ALL. In the treatment, we should pay attention to the hepatic condition of ones who are over 60 years old or after stem cell transplantation, attemps to avoid and treat VOD are warranted. Above all, When patients with refractory leukemia got remission, allogenic-SCT should be done as soon as possible