A predictive model for the clinical response to low dose ara‐C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia

Abstract

The response to treatment with low-dose ara-C was studied in 102 consecutive patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo-Pelger morphology and > or = 2 chromosomal aberrations. Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38.6% of the patients, with a response rate of > 50%, an intermediate group, 32.7% of the patients, with a response rate of 24%, and an unfavourable group, 28.7% of the patients, with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two-thirds of patients with MDS and MDS-AML by identifying patients who should not be treated with low-dose ara-C as well as patients with a relatively high probability of response.

Preferential cytogenetic response to continuous intravenous low-dose decitabine (DAC) administration in myelodysplastic syndrome with monosomy 7

“…This high response rate in patients with chromosome 7 abnormalities is in stark contrast to the notoriously low response rate of MDS patients receiving conventional low-dose therapy with AraC. 4 In summary, the optimal dose and schedule of DAC for a nonintensive, outpatient treatment of high-risk MDS patients may not yet be defined. The Bayesian design has not been uniformly accepted as the optimal methodology to identify treatment superiority.…”

Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet

“…The evidence on the use of LDAC has been drawn from systematic reviews of the literature and randomized controlled trials. [178][179][180][181][182][183][184][185][186][187] One hundred forty-one patients with one of the FAB-defined subtypes of MDS were included in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group randomized phase 3 study comparing LDAC (10 mg/m 2 subcutaneously twice daily for 21 consecutive days) vs supportive treatment. 183 The overall response rate to a single cycle of LDAC was 32%, with a median duration of response of 5.9 months (range, 1.4 to 33.5 months).…”

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

“…The control arm included the three most commonly used treatments in higher-risk myelodysplastic syndromes (best supportive care, low-dose cytarabine, or intensive chemotherapy). 6–15,17 …”