Angelo Canevari

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS

One hundred and five consecutive primary high‐risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0–3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12 h i.v. for 5 d, Ara‐C 120 mg/m2/12 h i.v. for 5 d (one or two courses). Patients were randomized to receive or not G‐CSF (5 μg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G‐CSF. The CT + G‐CSF patients had a significantly shorter duration of neutropenia (8 v 16 d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P < 0.05). 40 patients entered CR: 17 with CT and 23 with CT+G‐CSF. Responders underwent two consolidation courses with the same CT, followed by high‐dose Ara‐C (2 g/m2 every 12 h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse‐free survival 4.5 months). Eight responders received an allo‐BMT, six are alive in CR 7–57 months post‐transplant. Therefore allo‐BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G‐CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo‐transplantable cases by inducing higher remission rates and improving clinical conditions.

Pipobroman is safe and effective treatment for patients with essential thrombocythaemia at high risk of thrombosis

Summary. Essential thrombocythaemia (ET) is a disease associated with an elevated risk of thrombosis. This study evaluated the efficacy and safety of pipobroman (PB) in the long‐term control of ET patients who had, at diagnosis, one or more of the following currently known risk factors for thrombosis or haemorrhage (high‐risk patients): age > 60 years, history of thrombosis or haemorrhage, platelets > 1000 × 109/l. From 1978 to 2000, with a median follow‐up of 10 years, 118 previously untreated high‐risk ET patients (median age 62 years, range 25–82), were treated with PB at the starting dose of 0·8–1 mg/kg/d. All patients reached a platelet count < 600 × 109/l and 91% achieved a platelet count < 400 × 109/l. During follow‐up, 13 patients had thrombosis, with a 10‐year cumulative risk of 14%. Acute myeloid leukaemia, myelofibrosis and solid tumours occurred in three, two and seven patients with a 10‐year cumulative risk of 3%, 2% and 7% respectively. Actuarial survival at 20 years was 64% and the standardized mortality ratio was 1·1 (95% CI: 0·7–1·7), not statistically different from the general population (P = 0·54). Age was associated with a higher risk of death (P = 0·00009) and thrombosis (P = 0·003). The duration of PB treatment did not correlate with the occurrence of second malignancies. This study, with a median follow‐up of 10 years, demonstrates that pipobroman is effective and well tolerated. The low cumulative 10‐year risk of thrombosis, leukaemia and solid tumours indicates that pipobroman is an adequate treatment for patients with high risk ET.

Risk of leukemia in patients treated for Hodgkin's disease.

We reviewed 251 consecutive adult patients with Hodgkins disease treated at the Division of Hematology, Policlinico S. Matteo, Pavia, from January 1970 to December 1979, to assess the risk of development of acute leukemia. The median time of follow-up was 48 months (range 6-135). No leukemia occurred in 88 patients treated with radiotherapy or chemotherapy alone. Six acute non-lymphoid leukemias occurred in the group of 163 patients treated with MOPP and radiotherapy (crude rate of leukemia of 7.5 per 1000 person-years at risk). All cases were in clinical remission and off therapy; the latent period from initiation of therapy to onset of leukemia ranged between 30 and 90 months. The actuarial probability of leukemia at five and seven years was 2.9 and 4.7% for the entire group of patients, and 3.8 and 5.8% for the combination therapy group. All leukemias , except one, had a preleukemic phase lasting 1-12 months, with cytopenia and dysplastic marrow. The median survival after leukemia was 4.7 months.

Adult acute lymphoblastic leukemia. Response to therapy according to presenting features in 62 patients

Sixty-two adult patients with acute lymphoblastic leukemia (ALL) were treated with an induction regimen including vincristine, daunorubicin and prednisone (VDP) followed by CNS prophylaxis. Forty-five patients (72.5%) achieved complete remission (CR). The CR were maintained with daily 6-MP and weekly MTX. Monthly reinduction cycles with vincristine and prednisone (plus daunorubicin every three courses) were also given. Median duration of CR was 10.4 months. Overall survival was 17.4 months. The remission rate and length of CR were studied in relation to the clinical and hematological features present at diagnosis. CR rate was adversely influenced by age only over 40 and by tumoral presentation. The length of remission was negatively influenced by tumoral presentation, CNS involvement, high circulating blast count, L2 and L3 cytology, and T or B immunological phenotype. Multiple regression analysis confirmed the weight of FAB morphology in determining the length of remission. Among L2 adult patients, tumoral presentation appears to be the major unfavourable prognostic factor.

VP 16-213 and cytosine-arabinoside combination chemotherapy for refractory acute lymphoblastic leukemia in adults

Fifteen adult patients with refractory or relapsing acute lymphoblastic leukemia (ALL) received a 5-day remission induction regimen consisting of VP 16-213 (60 mg/m2 every 12 hr) and cytosine-arabinoside (100 mg/m2 every 12 hr) up to a maximum of three courses. The overall response rate was 60% (9/15), four patients (27%) achieving CR and five (33%) attaining PR. Responders were maintained with monthly courses of the same combination until progressive disease developed. The median duration of response was 4.5 months (2-12+ months). The regimen was relatively well tolerated. The major toxicity was hematologic. Non-hematologic toxicities included mild nausea and vomiting (11/15) and total alopecia (15/15). The results obtained with this combination are encouraging, in view of the poor prognosis associated with refractory or relapsing ALL in adults.

Growth Factors in the Therapy of Myelodisplasia: Biological Aspects

Growth factors (GF) are reported to play an important role in the therapy of myelodisplastic syndromes (MDS). After in vitro administration a consistent group of MDS may respond to GF but the possibility of differentiation, regulation or expansion of myelodisplastic clones following GF therapy is still a question to be answered as their optimum dose and combinations. To validate if in vivo treatment with GF, may promote the regulation or the recovery of myelopoiesis and/or modify the clonality of the responses, we gave G-CSF after intensive chemotherapy in high risk MDS and acute leukemia evolving from MDS patients. According to our data the use of G-CSF after intensive chemotherapy may improve the CR rate without increase of leukemic transformation. However the answer were clonal and the remission duration remained very short so we suggest to utilize this time to perform other therapeutic strategies such as, when possible, the BMT.

Unilateral Retinal Vasculitis Associated with Hairy Cell Leukaemia: Immunogenetic Study

This report describes a case of retinal vasculitis which occurred in hairy cell leukaemia and was localized only in the right eye. An immunogenetic study investigates the possible genetic association between vascular uveitis and hairy cell leukaemia.

Low-grade malignancy non-Hodgkin's lymphomas: prognostic relevance of their clinicopathologic heterogeneity.

We reviewed 182 consecutive adult patients with low-grade malignancy, non-Hodgkins lymphomas classified according to the Kiel classification, followed at the Division of Hematology, Policlinico S. Matteo, Pavia, from January 1975 to December 1981, to recognize, in each histopathologic type, important subgroups from the prognostic standpoint. Median follow-up was 36 months. No significant differences were observed in the response rate to conventional therapy (radiotherapy for localized disease, CVP for advanced stages) between the 4 cytologic types. The centrocytic-centroblastic lymphoma with diffuse nodal architecture showed an intermediate-grade malignancy (median survival, 50 months) and underwent cytologic progression to the high-grade malignancy centroblastic type in 10% of the cases. Large-cell centrocytic and polymorphic lymphoplasmacytoid lymphomas had a poor prognosis (median survival less than 30 months) when treated with conventional therapy for favorable histologies, and 6% of the cases transformed into the high-malignancy immunoblastic type. Patients with lymphocytic lymphoma with bulky mediastinum had a median survival of 20 months. The identification of these subgroups with a worse prognosis may have therapeutic implications.