The Role for Induction Chemotherapy and Allogeneic Stem Cell Transplant in Patients with Chronic Myelomonocytic Leukemia That Have Undergone Leukemic Transformation: A Single Center Experience

Background: Leukemic transformation is seen in approximately 10-20% of patients with chronic myelomonocytic leukemia (CMML). We carried out this study to analyze the clinical features and treatment outcomes in these patients.

Methods: After due IRB approval, 275 patients with WHO defined CMML seen at the Mayo Clinic from 1997 through 2012 were identified. All patients underwent bone marrow (BM) and cytogenetic evaluation at diagnosis and transformation. Patients were evaluated for leukemic transformation and their clinical and pathological information was retrospectively abstracted.

Results: Of 275 patients with CMML, 42 (15%) had documented leukemic transformation.  The median age at transformation was 68 years (range, 18-87); 21 (50%) were male and the median follow up was 70 months (range, 37 - 112) with 34 (79%) deaths recorded at last follow up. At initial diagnosis 13 patients (31%) had CMML-2. The distribution of  patient across different prognostic models was: Mayo prognostic model- 27 (65%) high risk, 14 (33%) intermediate Risk and 1 (2%) low risk; Global MD Anderson Score- 11 (26%) high risk, 11 (26%) intermediate-2 risk, 14 (34%) intermediate-1 risk and 6 (14%) low risk. Five (12%) patients presented with elevated white blood counts resulting in leukostasis (clinical blast crises). Ten of 36 (28%) evaluable patients had cytogenetic clonal evolution at transformation.

Twenty two (51%) patients with leukemic transformation received standard induction chemotherapy, 5 (12%) received hypomethylating agents (HMA) and the remainder were ineligible for further treatment. Fifteen (68%) patients treated with induction chemotherapy achieved a first complete remission (CR1) in comparison to only one (20%) with a HMA. The median survival after transformation for patients achieving CR1 was 28 vs. 2.4 months for the rest of the group (Fig 1, p<0.001). Seven (32%) patients who underwent induction chemotherapy eventually proceeded with allogeneic stem cell transplantation (SCT) (4 matched unrelated donor, 2 matched related donor and 1 Cord blood transplant), of which one (14%) relapsed shortly after SCT; the remainder are currently alive and disease free. Among patients achieving a CR1, the median survival for patients undergoing allogeneic SCT was not reached compared to 25 months for the remainder (Fig 2, p<0.001).

In a univariable analysis, receiving induction chemotherapy (p=0.016), achieving a CR1 (p<0.001) and undergoing an allogeneic SCT (p<0.001) were independent prognosticators predicting improved survival; however in a multivariable model, achieving a CR1 (p=0.002) and undergoing allogeneic SCT retained prognostic significance (p=0.01). 

Conclusion: Leukemic transformation from CMML is associated with poor outcomes. For eligible patients, induction chemotherapy followed by allogeneic SCT seems to offer the best chances for achieving durable remissions.

Fig 1

Fig 2