Abstract

The t(10;11)(p12–13;q14–21) is a very rare but recurring chromosomal translocation observed in patients with both ALL and AML resulting in the generation of a CALM–AF10 fusion gene. Although clinical features of CALM-AF10 positive ALL have been described, there are only few data about the clinical characteristics and outcome of AML patients. We have studied 18 AML patients treated in 11 French hematological centers. Patients were included in this study after an exhaustive survey in the main French hematological centers. Clinical and biological data were collected for 18 patients diagnosed between 01/1993 and 01/2008. The characteristics of patients were as follows: median age, 30y (10–77y); sex ratio (M/F) 1,25; median WBC count, 17.6 G/L (0.8–298) and 4 pts (22%) with WBC>100 G/L; median Hb, 9.4 g/L (5.4–12.6); median platelets, 84 G/L (10–238), median bone marrow blasts, 90% (35–98%). FAB subtypes were: 1 M0; 10 M1, 1 M2 and 6 M5. Extramedullary disease was found in 10 pts (56%) (gingival hypertrophy, 3/18; lymph nodes, 9/18; chloromas, 2/18; serous involvement, 2/18; hepatosplenomegaly, 1/18). Of note, 3 pts had previously received polychemotherapy for diffuse large B cell lymphoma (DLBCL) and 1pt for AML without cytogenetic analysis available at diagnosis. The t(10;11)(p12–13;q14–21) translocation was found as the sole chromosomal abnormality in 7 pts (39%) whereas 11 pts displayed additional abnormalities including high risk abnormalities (−7; 5q−; Ph+; 17p−) in 4 of them. Trisomies 4 and 19, frequently observed in our series, might be nonrandom secondary abnormalities in CALM-AF10 AMLs. In all cases, the presence of the CALM-AF10 rearrangement was confirmed either by RT-PCR or by FISH analysis. FLT3 mutations were screened in 6 samples but no FLT3-ITD mutation was detected. Immunophenotypic data showed that CD13, CD33, CD65, CD117, CD34, HLADR and MPO were expressed in 69%, 88%, 50%, 50%, 50%, 92% and 67% of cases, respectively. CD7 was also frequently expressed (9/11, 82%) whereas CD2, CD4, CD10 and CD19 were expressed only in a few cases. Induction chemotherapy using anthracyclines and aracytin was delivered in 17 patients, 3 of them received timed-sequential induction. At day 15, 8/14 pts receiving standard induction had more than 5% marrow blasts and received a second induction course. There was no early death and the response rate was 66% (11 CR + 1 CRi). Six patients underwent allogeneic stem-cell transplantation (Allo-SCT) (5 in CR1, 1 refractory), 4 pts consolidation chemotherapy alone and 2 pts autologous SCT while 1 patient died in CRi. Of note, the patient allografted with refractory disease achieved CR after allo-SCT and is alive at 12 months from diagnosis. 6 pts relapsed (3 after allo-SCT, 2 after auto-SCT and 1 after consolidation chemotherapy) and second CR was achieved in 5 but CR2 were short lasting except for two pts for which the duration of CR2 was 3 and 10 years, respectively. Among the 17 patients treated by induction chemotherapy, median overall survival was 18 months. With a median follow-up of 11 months (range, 2 to 181 months), the median remission duration and median OS for CR/CRi patients were 23 and 28 months, respectively. There were 3 long term survivors (> 3 years), 2 pts in CR1 who received chemotherapy only as consolidation therapy and one in CR3 after 2 allo-SCTs. CALM-AF10 AMLs are characterized by younger age, extramedullary involvement, and high relapse rate. Some cases may be therapy-related AMLs, secondary to chemotherapy for other hematological malignancies and particularly DLBCL. Although the prognosis is poor, long term response can be achieved in a subset of patients.

Disclosures: No relevant conflicts of interest to declare.

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