Thirty-seven patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Patients received 45 mg m -2 day -1 po of ATRA until complete remission (CR) was achieved, defined as: a) presence of less than 5% blasts in the bone marrow, with b) white blood cells >10 3 /mm 3 , c) platelets >10 5 /mm 3 and d) hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7%) patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days), was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS) were observed in 7 (19%), 6 (16%) and 4 (11%) patients, respectively. Thirteen (35%) patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 10 3 /mm 3 ) and six of these presented with new signs of coagulopathy after chemotherapy. Four (11%) patients died secondarily to intracerebral hemorrhage (IH) and two (5.4%) dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity). RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.
Correspondence
Introduction: Allogeneic Stem Cell transplantation from an HLA identical sibling is considered the treatment of choice for young pts. For pts without a suitable donor, immunosupressive treatment with cyclosporine (Csa) + prednisone (Pred) + Antithymocyte globulin (ATG) is an effective alternative treatment. In 1988, as ATG supply was not regular in our country, we decided to initiate a trial using only Csa +Pred to treat SAA without a matched sibling donor.
Material and Methods: All pts had the diagnosis of SAA according to established criteria (Camitta et al Blood1976; 48:63–70) and 95 pts had received previous treatment (androgens, Csa alone or steroids). Treatment: Csa: 12mg/kg/day BID from day(D)1- D8, then 7mg/kg/day BID until 1 year. After 1 year, Csa was slowly weaned (5% each month) until definitively stopped. Csa levels were maintained between 200-400ng/ml. Pred:2mg/kg/day from D1-D14 then 1mg/kg/day from D15- D45. From that day on Pred dose was weaned 20% each week until stopped. Prophylactic antibiotics were given according to common practice. Number of pts: 287. Period: 12/1988 to 01/2004. Age: 2-74y (Median: 22). Disease duration: 10–4015days (Median:100). Previous transfusions: 0-160UI (M:10). At diagnosis, granulocytes counts ranged from 0-3110/ul(M:540/uL) and platelet counts from 1000-53000/uL(M:11000/uL). Treatment evaluation was performed at 6weeks, 3,6 and 12 months and then yearly after. Definition of response: Type I: independence of red cells and platelets transfusions and improvement of hematological parameters (Hb>10g/dL, platelets>50.000/uL and granulocytes>1000/uL). Type II: Improvement of hematological parameters (not enough to reach the hematological counts previously specified) with or without dependence of blood transfusions. Type III: No evidence of improvement and dependence of blood transfusions.
Results: Overall survival is 63% with a median follow-up of 7 y(6months- 15 years). Response to treatment: TypeI was achieved in 138pts (48%) and all but one pt is alive. These pts have a normal life, free of infections and are transfusion independent. TypeII occurred in 21 pts(7,3%) and 13 pts are alive with only 1 pt dependant of red blood cell transfusions every 45 days. TypeIII occurred in 128pts (44%) and 50 pts are still alive. Most pts responded between 3 and 6m of treatment. Response to treatment was significantly influenced by: Granulocytes at diagnosis >500/uL (p=0,0001); platelets at diagnosis >12000/ul (p=0,01); age>22y(p=0,0061) and previous transfusions < 10UI (p=0,008). Granulocytes at diagnosis >500/uL (p=0,02), platelets at diagnosis >10000/uL (p=0,01)and disease duration >45 days (p=0,02) significantly affected survival. Toxicity was tolerated and well controlled. Hypertension, gingival hypertrophy and diabetes mellitus were frequent complications. Relapse occurred in 19% (31pts) and twenty-two pts(70%) responded to a second treatment using the same drugs but 9pts became cyclosporine dependant. Clonal or malignant disease occurred in 5 pts (2AML and 3 PNH).
Conclusion: This data demonstrates that Csa +Pred is an effective treatment for pts with SAA without a suitable donor. Pts may become free of infections and transfusion independent and are able to live normal lives even though their blood counts are still subnormal
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