Biomedical subjects

M Lazzarino

Publications and source records attributed to M Lazzarino.

At least 127 records · Page 7Linked to original sources

PubMed1984

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.

Adolescent↗

PubMed1984

Clinical utility of terminal deoxynucleotidyl transferase and adenosine deaminase determinations in adult leukemia with a lymphoid phenotype.

A prospective study was done to assess the clinical utility of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) assays in adult leukemia with a lymphoid phenotype. The study population consisted of 58 patients with adult lymphoblastic leukemia (ALL) at onset, 12 with lymphoblastic lymphoma, 15 with acute unclassifiable leukemia (AUL), and 30 with lymphoid or mixed acute phase of Philadelphia chromosome-positive (Ph' +) chronic myelogenous leukemia (CML). TdT was present in all cases of T-ALL, in 90% of non-T, non-B ALL, and absent in B-ALL; the ADA activity was significantly higher (P less than .01) in T-ALL. TdT was found in 75% of lymphoblastic lymphomas, in 78% of lymphoid, and in 50% of mixed CML transformations; higher ADA activity correlated with TdT positivity in AUL and CML blastic transformations (P less than .001). TdT-positive ALL had a better chance of response to therapy than TdT-negative ALL (P less than 0.01), but survival was not statistically different. TdT was undetectable in the peripheral blood of patients with ALL in complete remission and within the normal range in bone marrow (0.1%-8% of nucleated cells); median ADA activity was as in control subjects. Relapsing ALL patients had TdT and ADA enzymatic activities as before therapy; TdT immunofluorescence test (IF) was positive in 69% of bone marrow and in 100% of CNS relapses. Twenty percent of TdT-positive ALL at onset became TdT-negative in bone marrow at relapse. TdT IF test was instrumental in detecting meningeal leukemia but neither TdT nor ADA could be used as indicators of complete remission or impending relapse because TdT-positive cells were present in normal marrows and wide fluctuations of TdT IF values and of ADA activity were observed in remission.

Acute Disease↗

PubMed1982

Pathogenetic significance of "pure" monosomy 7 in myeloproliferative disorders. Analysis of 14 cases.

Monosomy 7 is frequent in acute myeloid leukaemia (AML) and in preleukaemic dysmyelopoietic syndromes but often it is not the only chromosome anomaly associated with these conditions. We report 14 patients with "pure" monosomy 7 and their clinical and haematological data are analysed in order to clarify the possible implications of this chromosome anomaly. The following points are considered: 1) In spite of the apparent variability of clinical forms in which monosomy 7 is found, several characteristics are common to all monosomy 7 patients, i.e. the presence of a preleukaemic phase and blood and marrow features suggesting the early involvement in the disease of all marrow cell lines. The different diagnoses associated with monosomy 7 are correlated with different steps of a unique myeloproliferative disease whose typical course can be reconstructed. 2) Monosomy 7 has a negative prognostic value. When it is found in a preleukaemic disorder it indicates a high risk of progression to AML, while in AML it implies recurrent infections, poor response to therapy and short survival. 3) The significance of the lack of Colton blood group antigens in monosomy 7 patients is discussed, with particular regard to the fact that the patients in whom this lack was found are the only ones who had not received transfusions in the months before the tests were done. 4) The finding of defective neutrophil chemotaxis in monosomy 7 patients is confirmed and the clinical importance of this fact is emphasized. 5) The data on the 14 patients support the opinion that AML, in general, is heterogeneous in origin. It is postulated that monosomy 7 is a marker of a specific pathogenetic pathway of AML, which implies the beginning of the malignancy in a pluripotent stem cell.

Adult↗

PubMed1982

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

We reviewed 251 consecutive adult patients with Hodgkin's 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↗

PubMed1982

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.

Adolescent↗

PubMed1982

Prognostic significance of terminal transferase and adenosine deaminase in acute and chronic myeloid leukemia.

We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.

Adenosine Deaminase↗

PubMed1979

Transposition of 9q34 and 22 (q11toqter) regions has a specific role in chronic myelocytic leukemia.

Six cases are reported of variant Ph' translocations found among 240 patients with Ph'-positive CML. Five cases had a three-chromosome rearrangement involving, in addition to chromosomes 9 and 22, chromosomes 7, 4, 2(two), and 3, respectively, and one case had a two-chromosome rearrangement 22/5. A review of the literature revealed that three- and two-chromosome variant Ph' translocations are observed with equal frequency. It is postulated that all variant translocations are indeed three-chromosome rearrangements, that the specific event for the formation of the Ph' chromosome is the reciprocal translocation 9/22, and that the transposition of regions 9q34 and 22 (q11toqter), plays a major role in the development of CML.

Adult↗

PubMed1975