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 (

Kantarjian H, Cancer 2006;106:1794
;
Steensma DP, ASCO 2008:Abstr7032
) and open-label studies (
Aribi A, Cancer 2007;109:713
;
Wijermans PW, Leuk Res 2008;32:587
) have reported that decitabine (DACOGEN, Janssen Cilag Farmaceutica S.A. and Eisai Inc.) is effective in the management of CMML.

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.

VariableCMML (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%) 
VariableCMML (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%) 
View Large

Topics:
decitabine, leukemia, myelomonocytic, chronic, complete remission, cancer, brachial plexus neuritis, partial response, prostatic hypertrophy risk score, bcr-abl tyrosine kinase, dysplasia, leukemia, myelocytic, acute

Disclosures: Iastrebner:Janssen Cilag Farmaceutica S.A.: Speakers Bureau.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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