The dose of total body irradiation (TBI), and GvHD prophilaxis have a crucial role on relapse risk and survival after BMT for leukaemia.
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Biomedical subjects
Publications and source records attributed to T Lamparelli.
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Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily, 33 patients were treated with r-alpha-2a, 34 with r-alpha-2b, and 25 with alpha-Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.
One hundred and seventeen patients undergoing allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (n = 18) or leukemia (n = 99) who were alive on day +180, were analysed for the incidence and severity of chronic graft-versus-host disease (cGVHD), developing before or after discontinuation of cyclosporin A (CSA). All patients received CSA for GVHD prophylaxis for 94 to greater than 988 days post-BMT. cGVHD developed in 74 patients (63%) before CSA discontinuation (de novo n = 12, progression from acute GVHD n = 42, following resolution of acute GVHD n = 20). CSA was discontinued in 112 patients: electively (n = 80), because of toxicity (n = 8), or following relapse of leukemia (n = 24). In five patients CSA was never discontinued. After discontinuation of CSA, progression or de novo cGVHD was seen in 25 patients, with a significant difference in patients treated for more or less than 150 days (8% vs 41%, p = 0.0007). In 15 patients CSA had to be re-instituted and in 14 it could be discontinued a second time. Overall 111/117 (94%) patients have finally discontinued CSA. In conclusion cGVHD will progress or appear de novo in 41% of patients receiving CSA for less and in 8% of those receiving CSA for more than 150 days respectively, indicating that the drug should be administered for at least 5 months post-BMT. Most patients (94%) will eventually become CSA independent.
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Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.
This is a review of current treatment for hairy cell leukemia (HCL). Data for this analysis were obtained from the Italian HCL Registry, as well as from other published series. We have given space to the impact of interferon and pentostatin on the management of this disease. Other issues are also discussed, such as the relevance of achieving a complete remission with respect to overall and relapse-free survival. We include a final section on recommendations which may prove useful in designing an appropriate therapeutic strategy.
BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.