High efficacy and low toxicity of APL induction with concurrent idarubicin/ATRA followed by a novel and simplified outpatient post-remission therapy using single doses of idarubicin and intermittent ATRA.

Acute promyelocytic leukemia (APL) is one of the most curable myeloid malignancies because of its great sensitivity to all-trans retinoic acid (ATRA) and response to anthracycline therapy. In an attempt to simplify post-remission therapy, deliver adequate dose of anthracycline and reduce treatment related toxicity, we entered 26 consecutively newly diagnosed, previously untreated APL patients in a pilot treatment program consisting of concurrent induction using idarubicin/ATRA followed by an exclusive outpatient post-remission therapy using single dose of idarubicin and intermittent ATRA, every 4 weeks. Of 25 evaluable patients, two (8%) died early during induction due to hemorrhagic complications, and 23 (92%) achieved complete remission. Overall survival at 4.2 years was 90% (CI 76.4-100), and 3.6 years disease-free survival was 78% (CI 60.6-95.4). The treatment outcome of this program is encouraging; however, the result of this study needs to be validated in larger cohort of patients and optimally in a randomized comparison with other current post-remission approaches.

Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution.

Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT1), median age was 11.5 years (range, 0.16-45 years). BMT1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, beta-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT2) was 14 years (range, 0.41-46.7 years). Indications for BMT2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT1 to BMT2 interval was 13 months (range, 1-107 months). For BMT2, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT1 and chemotherapy conditioning +/- ATG for those who received radiation containing conditioning at BMT1. Bone marrow was the stem cell source for all patients at BMT2 and all except three autologous peripheral stem cell transplantation patient at BMT1. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT2. At a median follow up of 36 months after BMT2, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD +/- 9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT1-BMT2 interval of > or = 6 months (P=0.0007) and age at BMT2 < or = 10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT2 using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age < or = 10 years and with an interval of > or = 6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

Leukemic synovitis as a presentation of myelomonocytic blast crisis of chronic myeloid leukemia.

We describe a patient with a 2-month history of right shoulder monoarthritis and fever as the presenting symptoms of a subsequent diagnosis of chronic myeloid leukemia in blast crisis. Imaging studies showed changes consistent with leukemic infiltration of the soft tissues around the right shoulder joint and the proximal humerus. Immunophenotypic and morphologic analysis of the large number of cells obtained from the synovial fluid confirmed the shoulder synovitis to be an extramedullary manifestation of myelomonocytic blast crisis of chronic myeloid leukemia. The patient was not a candidate for aggressive chemotherapy treatment because of her poor overall condition, and she had no compatible donor for allogenic bone marrow transplantation. Her painful arthropathy was refractory to standard pain management but she achieved excellent pain relief with palliative radiation therapy. We conclude that the involvement of extramedullary sites by chronic myeloid leukemia blast cells can predate hematological blast crisis in some of chronic myeloid leukemia cases. Also, painful leukemic synovitis can be managed by low dose radiotherapy in a candidate who is refractory to chemotherapy and other medical therapy.