We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)/acute lymphoblastic leukemia ¼ 25/19) who underwent allogeneic transplantation at our center between 11/1990 and 04/2004. The median leukemic blasts was 25% and age 28 years (range, 3-56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body irradiation and etoposide (Bu/Cy/VP, n ¼ 22; TBI/Cy/VP, n ¼ 17; others, n ¼ 5) followed by marrow or peripheral blood transplant (n ¼ 23/21) from unrelated or related donors (n ¼ 28/16). All patients had graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. One patient experienced late graft failure. Severe acute-GVHD and chronic-GVHD appeared in eight and 14 patients, respectively. Thirteen patients (30%) remain alive after a median of 25.3 months (range, 2.4-134.1); with 31 deaths, mostly from relapse (n ¼ 15) and infections (n ¼ 12). Overall survival (OS) and progression-free survival (PFS) at 5 years was 28 and 26%, respectively. OS and PFS were significantly better with blasts p20% and time to transplant p1 year while transplant-related mortality was less with the use of TBI. We conclude that patients with refractory leukemia can benefit from allogeneic BMT, especially with p20% marrow blast.
Warfarin treatment requires regular and proper monitoring to avoid overanticoagulation and at the same time to prevent thromboembolic complications. This study assessed the quality of warfarin anticoagulation at Princess Marina Hospital in Botswana. This cross-sectional study consecutively enrolled patients who were on warfarin for at least 3 months in the outpatient medical clinic. The level of anticoagulation was determined by the time in therapeutic range (TTR) using the Rosendaal method that calculates the percentage of days when the international normalized ratio is in the therapeutic range (2.0-3.0). Poor anticoagulation control was defined as an estimated TTR <65%. We performed univariate and multivariate logistic regression to assess predictors of poor anticoagulation control. Of total, 410 (68.8% women) patients whose median age was 46 (interquartile range [IQR], 35-58) years were enrolled. Indications for warfarin included mechanical heart valves, 185 (45.1%); deep vein thrombosis, 114 (26.8%); and atrial fibrillation, 68 (17.8%). Of the 2004 tests (an average of 4.9 tests per patient) assessed, only 20% of the tests were within the therapeutic range. The median TTR was 30.8% (IQR, 15.2-52.7). Most (85.1%) patients had poor anticoagulation control. Cigarette smoking and pulmonary hypertension perfectly predicted poor anticoagulation. Hypertension was a predictor of poor anticoagulation control (adjusted odds ratio = 2.24; 95% confidence interval: 1.02-4.94). The quality of anticoagulant therapy with warfarin in Botswana patients is poor. The evidence calls for efforts to improve the level of anticoagulation control among patients on warfarin in Botswana.
The introduction of tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) led to a dramatic change in the role of allogeneic stem cell transplantation (SCT) with a rapid decline in the number of patients receiving SCT in first chronic phase (CP1). We evaluated 68 consecutive patients in all phases of CML (male/female = 39:29, 27 in CP1), who received SCT from related/unrelated donors (related/unrelated = 23:45) under myeloablative or reduced intensity conditioning (MAC/RIC = 45:23). Forty-eight patients (71 %) received TKIs pre-SCT, 20 patients post-SCT (29 %). Overall survival (OS) of CP1 patients achieved a plateau of 85 % at 10 months. Relapse-free survival (RFS) of CP1 patients was 85 % at 1 and 2 years, and 81 % at 5 years. Multivariate analysis showed adverse OS and RFS for patients transplanted >CP1 (hazard ratio (HR) = 6.61 and 4.62) and those who had grade III-IV aGvHD (HR = 2.45 and 1.82). Patients with advanced CML had estimated OS of 65 and 47 %; and RFS of 41 and 32 % at 1 and 2 years respectively. Therefore, for patients with advanced CML phases, allogeneic SCT provides an acceptable chance of cure. Transplant research should focus on improving conditioning regimens and post-SCT management for this subgroup of CML patients.
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