Allogeneic Transplantation for Acute Myeloid Leukemia (AML) M2 with Translocation (8;21) and CD56 Positivity Is Effective Even for Patients with Relapsed Disease.

Background:

Patients with AML-M2 with t (8;21) generally have a good prognosis. However, the subset who have CD56 expression on their leukemic cells have poor prognosis, with frequent extramedullary involvement, short initial remissions, and high mortality. To date, little is known about the outcomes after allogeneic transplantation for patients with these unique characteristics.

Methods:

The Loyola transplant registry was searched for patients who underwent allogeneic transplantation at Loyola University Chicago Medical Center, Illinois during the period between June, 1998 and May, 2004 with these features. Patients were included in the analysis if their bone marrow examination at presentation met the FAB criteria for AML-M2; t (8;21) (q22;q22) was present by conventional karyotyping or by fluorescence in-situ hybridization (FISH); and CD56 expression was demonstrated by flow cytometric analysis of the leukemic blasts.

Results:

Five patients were identified; median age was 40 years (range 26–57 years); three were male. Median time from diagnosis until transplant was 12 months (range 3–93 months). Two patients had extramedullary diseases manifested by paraspinal and orbital granulocytic sarcoma at presentation or at relapse. One patient had 9q- in addition to the t (8;21). Patients had received a median of three prior therapy regimens (range 1–10) before transplant, including one patient who underwent high-dose chemotherapy and autologous stem cell transplant. Despite this, 4/5 patients had relapsed or refractory disease at transplant. Preparative regimens were total body irradiation 12Gy plus cyclophosphamide 120mg/kg in four patients and IV busulfan 14mg/kg plus cyclophosphamide 120 mg/kg in one; graft versus host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Three patients received grafts from matched unrelated donors; the rest from siblings. Three patients received bone marrow ranging from 2.0–4.4 x10⁸/kg WBC and two received peripheral stem cells 4.0–6.07 x10⁶/kg CD34+. The median time to neutrophil engraftment (the first of three consecutive days with absolute neutrophil count above 500/ml) was 14 days (range 12–17). The median time to platelet engraftment (the first of seven days with platelet count above 20,000/ml without transfusion) was 15 days (range 11–29). At day 100, all assessable patients (N=4) were in remission by bone marrow morphology with undetectable t (8;21) by FISH. As of August 2004, three patients survive at a median follow-up of 21 months (range 2–74 months); all remain in complete remission. Grade IV GVHD of skin occurred in one patient and grade II GI GVHD occurred in two. One patient, who received ten chemotherapy regimens over a 93-month period before transplant, died from pneumonia and venoocclusive disease of the liver; the other died from aspergillosis.

Conclusions:

Long-term disease free survival is possible with allogeneic transplant among patients with AML-M2 with t (8;21) and CD56 expression despite relapsed or refractory diseases. Clinicians should consider allografts, even from unrelated donors, early in the course of the disease to avoid the likely relapses after conventional therapy and to reduce the morbidity and mortality often seen in heavily pre-treated patients.