Observational study of iron overload as assessed by magnetic resonance imaging in an adult population of transfusion-dependent patients with beta thalassaemia: significant association between low cardiac T2* < 10 ms and cardiac events.

BACKGROUND: Thalassaemia major patients usually die from cardiac haemosiderosis. Improved strategies are required to modify this risk. AIMS: To assess the significance of cardiac iron overload in patients with beta thalassaemia. METHOD: Observational study of cardiac iron overload as assessed by magnetic resonance imaging (MRI) cardiac T2* relaxometry in 30 adult patients with transfusion-dependent beta thalassaemia. RESULTS: 11/30 patients (37%) had cardiac T2* < 10 ms, 8/30 (27%) in range 10-20 ms and 11/30 (37%) > 20 ms. There was significant inverse correlation between T2* values and values for serum ferritin (SF) and liver iron concentration (LIC) and positive correlation with left ventricular ejection fraction (LVEF). Median LVEF values were 49% in patients with T2* < 10 ms and 58% in patients with T2* > 10 ms (P = 0.02). Very low T2* values <10 ms were strongly associated with the occurrence of cardiac events (congestive heart failure, arrhythmia, cardiac death): occurring in 5/11 patients with T2* < l0 ms and in 0/19 in patients with T2* > 10 ms (P = 0.003 Fisher's exact test; P = 0.002 log rank Kaplan-Meier time to event analysis). There was no significant association between T2* < 10 ms or cardiac events and traditional measures of iron overload, such as SF levels >2500 mg/L and LIC (evaluated at thresholds of >7 or >15 mg/g dry weight). CONCLUSION: Very low cardiac T2* values <10 ms are common in adults with beta thalassaemia and are significantly associated with risk of cardiac events. This permits the use of individually targeted chelation strategies which are more effective in removing cardiac iron.

Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait.

Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.

Sequential standard dose mitoxantrone and cytosine arabinoside for newly diagnosed adult acute myeloblastic leukemia.

Twenty one adult patients with previously untreated acute myeloblastic leukemia (AML) were treated with sequential mitoxantrone and standard dose cytosine arabinoside remission induction therapy. The median age was 33 years (range 17-56 years). Complete remission (CR) was achieved in 80% (17/21 cases) and 76% (16/21 cases) achieved CR after one course of induction therapy. The median duration of disease free survival was 9 months with an actuarial disease free survival of 22% at 43 months. The non-hematological toxicity was acceptable. We conclude that sequential mitoxantrone and cytosine arabinoside combination therapy is an effective antileukemic regimen which produces high CR rates in previously untreated adult patients with AML.

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.