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Biomedical subjects

R Battista

Publications and source records attributed to R Battista.

At least 37 records · Page 2Linked to original sources

Short term therapy (STT) for acute myelogenous leukaemia (AML).

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.

Adolescent↗

Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia.

Between 1979 and 1987, 82 adults (age 14-71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m2) and cyclophosphamide (total 2.5 g/m2). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%-89%). Factors affecting favourable CR achievement were age less than 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P less than 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%-51%). CR duration correlated significantly with absolute blast cell count (15 x 10(9)/l or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%-46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.

Adolescent↗

Long-term outcome of adults with acute myelogenous leukaemia: results of a prospective, randomized study of chemotherapy with a minimal follow-up of 7 years.

In a prospective study running between 1981 and 1983, a group of 156 adult (under 60 years of age) patients with de-novo acute myelogenous leukaemia were randomly assigned to receive a daunorubicin, cytosine arabinoside and thioguanine combination or a regimen containing lower dosages of these drugs but also containing etoposide and vindesine. Patients who entered complete remission received maintenance therapy for 2 years. The survival and remission duration curves of the two groups were exactly superimposable and for this long-term analysis all patients have been considered together. The follow-up times range between 84 and 104 months. Actual survival at 7 years is 15% (95% confidence intervals 9-20%), with a stable curve thereafter. Actual probability of continuous complete remission at 7 years is 22% (95% C.I. 13-31%) with a stable curve beyond that point. These findings, similar to those of the few other studies of chemotherapy with comparable follow-up times, suggest that only a small fraction of adult patients become long-term survivors, irrespective of the precise type or amount of antineoplastic agents administered.

Adolescent↗

Clinical value of PCR in diagnosis and follow-up of leukaemia and lymphoma: report of the third Workshop of the Molecular Biology/BMT study group.

The proceedings of the third workshop of the molecular biology/bone marrow transplantation (BMT) study group held in January 1991 in Verona, Italy. This workshop was convened to review progress in the application of molecular techniques to the diagnosis and follow-up of patients with chronic myeloid leukaemia (CML) as well as other haematologic malignancies. The results of polymerase chainreaction studies in 157 CML patients 1-90 months post BMT suggest that leukaemia is frequently detectable for the first 12 months but rarely detected thereafter except in patients known to have a high risk of relapse. In the acute leukaemias and lymphomas there is a rapidly increasing number of leukaemia-specific as well as clone-specific molecular markers now available for the detection of minimal disease. It may be possible to coordinate multi-center prospective studies to investigate the role of these markers in the diagnosis and follow-up of haematologic malignancies.

Bone Marrow Transplantation↗

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.

Adolescent↗

Cytogenetic and clinical studies in acute promyelocytic leukemia (M3) and cytologic M3 variant (M3V).

Cytogenetic specimens were obtained from bone marrow 24-hour cultured cells in 22 patients with acute promyelocytic leukemia, including six with microgranular variant. A t(15;17) was identified in 10-100% of metaphase cells from 13 patients. We have found no correlation between complete remission percentage and karyotype. Our data suggest that each laboratory, as far as M3 and M3V are concerned, must study its own culture time as it relates to numerous parameters involving tumoral cell kinetics.

Adolescent↗

Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes.

Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved.

Alkaline Phosphatase↗

Treatment of the lymphoid blast crisis of chronic myeloid leukemia.

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.

Adult↗

Relationship of serum lactate dehydrogenase level with first remission length in adult acute lymphocytic leukaemia.

Several features have a prognostic value in adults with acute lymphocytic leukaemia (ALL). However, in about two-thirds of all cases prognosis remains quite variable, with a substantial number of early relapses. This study shows in 118 adult patients who attained complete remission (CR) between 1978 and 1984 that pretreatment serum total lactate dehydrogenase (LDH) activity was inversely correlated with first CR length. The prognostic value of LDH was higher than that of any other features both in univariable and in multivariable analysis. The value was significant in the whole series as well as in patients who lacked other high risk features. Among non-high risk and low-WBC count cases, patients with LDH less than or equal to 500 U/l had a median first CR duration of 27 months, and a projected 5-year relapse free survival of 36%, versus 9 months and 12% of patients with LDH greater than 500 U/l. These results fit well with the results of a study of ALL in children, and suggest that pretreatment serum total LDH activity is an important risk determinant in adult ALL.

Adolescent↗

Preliminary observations on intravenous idarubicin (4-demethoxydaunorubicin) in the chronic and accelerated phase of chronic myelogenous leukemia.

The study included 13 patients with chronic myelogenous leukemia (8 in the chronic phase with high WBC counts at onset, and 5 in the accelerated phase, poorly responding to conventional drugs for the chronic phase). They were treated with 4-demethoxydaunorubicin (idarubicin), a new anthracycline analog more active than daunorubicin (DNR) and doxorubicin (DX) in experimental tumor models which offers a higher therapeutic index than existing anthracyclines. Idarubicin was administered i.v. at the dose of 8 mg/m2 on days 1, 3 and 5. All patients in the chronic phase (8/8) developed significant leukopenia. Five of these 8 patients showed complete reduction of splenomegaly, and 4 of hepatomegaly as well. In all the other cases, hepato-splenomegaly was reduced by more than 70%. Three of the 5 patients in the accelerated phase of chronic myelogenous leukemia also showed massive cytolysis. More important, all of them showed complete or major reduction of hepato-splenomegaly and renewed responsiveness to conventional drugs for the chronic phase of the disease. Idarubicin was fairly well tolerated by all patients with only minor gastrointestinal side effects and no liver damage or acute cardiotoxic effects. These findings indicate that idarubicin--although it cannot replace established drugs for the chronic phase of the disease--represents an added therapeutic resource for producing rapid cytolysis at onset and, above all, in the accelerated phase of chronic myelogenous leukemia.

Administration, Oral↗

Treatment of 49 unrandomized patients with advanced Hodgkin's disease.

Forty-nine patients with previously untreated advanced Hodgkin's disease were treated in our Institution between 1973 and 1981. Treatment modalities of these patients were reviewed, and they were divided into 3 groups according to the treatment employed: 13 patients received MOPP only, 22 patients received MOPP plus involved field radiotherapy, and 14 received alternating MOPP/ABVD chemotherapy. The response rates for the 3 groups were respectively 38.5%, 63.6% and 78.6%. A longer follow-up is needed to assess a significant difference in survival curves. The advantages of adjuvant radiotherapy and alternating non-cross-resistant drugs in advanced Hodgkin's disease are discussed.

Adolescent↗