Abstract The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.
Background: Myelodisplastic syndromes (MDS) are an heterogeneous group of hematologic that frequently progress in acute myeloid leukemia (secondary AML, s‐AML). The hypomethylating agents azacitidine (AZA) and decitabine (DAC) are currently approved for the treatment of several specific subtypes of MDS and AML. Aims: Our aim is to suggest that DAC has a favourable efficacy and safety profile as rescue therapy after AZA failure Methods: We report a short case series of 4 patients referred to our institution with s‐AML occurring after MDS and MDS/MPN in accelerated phase treated with DAC following AZA failure used for MDS phase treatment. At the time of diagnosis, median age of patients was 73 (range 68‐78), all patients were Intermediate‐2 according to IPSS and they had RBC transfusion dependency. All patients underwent blood cell count samples, bone marrow biopsy and conventional cytogenetic assays to confirm diagnosis. Results: The 1 st patient was a 78‐years‐old woman with anemia (red blood cell transfusion dependency about 4‐5 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS‐EB‐2. Cytogenetic analysis showed a normal karyotype. She started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 11 courses the patient showed treatment failure with progression to AML (hyperleukocytosis WBC 150.000/microL, bone marrow blasts 40% and monosomy 8), thus she started treatment with decitabine iv at 20 mg/sm for 5 days in 28‐day cycles plus hydroxyurea. A bone marrow biopsy done after 4 and 8 cycles showed 10% and 8% of blasts, respectively. After 9 th cycle she died due to chronic obstructive pulmonary disease worsening. The 2 nd patient was a 72‐years‐old man with thrombocytosis and anemia (red blood cell transfusion dependency about 1‐2 RBC units/month) and 15% of bone marrow blasts diagnostic for MDS/MPN in accelerated phase. He started treatment with azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 24 courses of azacytidine he showed progression to AML (bone marrow blasts 30% and fibrosis), thus he started decitabine iv at 20 mg/sm for 5 days in 28‐day cycles. After 1st cycle the patient obtained a transfusion indipendency lasted for the following 3 cycles. After 4 th cycle he developed pancytopenia, therefore a BM assay showed 50% of blasts. Finally the patient died for infectiuos complications. The 3 rd patient was a 68‐years‐old woman with a diagnosis of MDS‐EB‐2 (bone marrow blasts 15%), normal karyotype and a red blood cell transfusion dependency of about 1‐2 RBC units/month. She started azacytidine sc at 75 mg/sm/day for 7 days in 28‐day cycles. After 32 courses the disease progressed to AML (70% of blasts), thus she started therapy with decitabine 20 mg/sm for 5 days every 28 days achieving a partial response. At the end of 4th cycle she died due to cerebral hemorrhage. The 4 th patient was a 74‐years‐old man treated with azacitidine (75 mg/sm for 7 days every 28 days) for a MDS‐EB‐2 (bone marrow blasts 10%, normal karyotype. He had a red blood cell transfusion dependency of about 1‐2 RBC units/month). After 10 cycles of azacytidine he showed therapy failure with progression to AML (bone marrow blasts 80%), so he started decitabine 20 mg/sm for 5 days every 28 days, discontinued after 2 courses due to clinical worsening Summary/Conclusion: In this short monocentric case series DAC demonstrated a favourable efficacy and safety profile as rescue therapy after AZA failure, also improving survival (median OS 7 months).
