Abstract
Background: Epigenetic therapy with hypomethylating agents has recently been approved for the treatment of myelodysplastic syndromes (MDS) in Argentina. Chronic Myelomonocytic Leukemia (CMML) is a hybrid disorder characterized by myeloid proliferation and erythroid-megakaryocytic dysplasia. Subgroup analyses (
Study objective: To compare the clinical and hematological improvement with decitabine among patients with CMML to those with other MDS subtypes.
Methods: We enrolled patients with MDS who received decitabine between July 2007 and June 2008 at 17 centers in our country. Inclusion criteria were ≥18 years of age, de novo or secondary MDS and an International Prognosis Scoring System (IPSS) score ≥0.5. Exclusion criteria were diagnosis of acute myeloid leukemia (AML) or other progressive malignant disease. Patients with prior therapy for MDS/CMML were not excluded. Patients were categorized as having CMML or another sub-type of MDS according to FAB/WHO criteria. All pts received decitabine 20 mg/m2 IV over 1 hour once daily for 5 consecutive days repeating every 4 weeks. Overall improvement rate (complete response + marrow complete response + partial response + hematologic improvement) was compared between cohorts with chi-square and Fisher’s tests.
Results: There were 11 patients with CMML and 27 patients with other subtypes of MDS. Demographic characteristics are summarized in the table. All CMML patients were BCR/ABL negative. Three patients had CMML type II (WHO classification, Blasts ≥10% in marrow and/or ≥5% in peripheral blood) and 8 had CMML type I. Four patients with CMML had proliferative features with WBC >13000/mm3 and splenomegaly at the time of diagnosis. The overall response was 73% in patients with CMML and 33% in patients with other MDS sub-types (p=0.003). Median time to first response in CMML pts was 2 cycles. Tolerability was acceptable in both groups with no significant differences.
Conclusion: Although our study group is small, decitabine demonstrated marked activity in CMML. Additional study of decitabine therapy in CMML is warranted.
| Variable . | CMML (N=11) . | Other MDS Subtypes (N=27) . |
|---|---|---|
| * (p=0.003) | ||
| Age, Median | 67 | 67 |
| Male, n (%) | 9 (82%) | 18 (67%) |
| IPSS Score, n (%) | ||
| Intermediate-1 | 7 (64%) | 12 (44%) |
| Intermediate-2 | 2 (18%) | 1 (4%) |
| High-Risk | 2 (18%) | 14 (52%) |
| No. (%) with Prior Therapy | 8 (73%) | 23 (85%) |
| No. of Cycles, Median (Range) | 4 (2–6) | 3 (1–8) |
| Treatment Response, n (%) | ||
| Overall Improvement (CR+PR+mCR+HI)* | 8 (73%) | 9 (33%) |
| Complete Response (CR) | 1 (9%) | 2 (7%) |
| Partial Response (PR) | 1 (9%) | 1 (4%) |
| Marrow Complete Response (mCR) | 2 (18%) | 0 |
| Hematologic Improvement (HI) | 4 (36%) | 6 (22%) |
| Stable Disease (SD) | 0 | 2 (7%) |
| Failure (Progressive Disease or Death) | 1 (9%) | 14 (53%) |
| Non-evaluable | 2 (18%) | 2 (7%) |
| Variable . | CMML (N=11) . | Other MDS Subtypes (N=27) . |
|---|---|---|
| * (p=0.003) | ||
| Age, Median | 67 | 67 |
| Male, n (%) | 9 (82%) | 18 (67%) |
| IPSS Score, n (%) | ||
| Intermediate-1 | 7 (64%) | 12 (44%) |
| Intermediate-2 | 2 (18%) | 1 (4%) |
| High-Risk | 2 (18%) | 14 (52%) |
| No. (%) with Prior Therapy | 8 (73%) | 23 (85%) |
| No. of Cycles, Median (Range) | 4 (2–6) | 3 (1–8) |
| Treatment Response, n (%) | ||
| Overall Improvement (CR+PR+mCR+HI)* | 8 (73%) | 9 (33%) |
| Complete Response (CR) | 1 (9%) | 2 (7%) |
| Partial Response (PR) | 1 (9%) | 1 (4%) |
| Marrow Complete Response (mCR) | 2 (18%) | 0 |
| Hematologic Improvement (HI) | 4 (36%) | 6 (22%) |
| Stable Disease (SD) | 0 | 2 (7%) |
| Failure (Progressive Disease or Death) | 1 (9%) | 14 (53%) |
| Non-evaluable | 2 (18%) | 2 (7%) |
Disclosures: Iastrebner:Janssen Cilag Farmaceutica S.A.: Speakers Bureau.
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