Guglielmo Castelli

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.

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.

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.

Immunoblastic lymphoma: a clinicopathologic study with emphasis on the cases intervening during or following other disorders.

Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26 %) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenströms disease, lymphoplasmacytoid lymphoma and Hodgkins disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyers ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67 %). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37 % and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkins lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.