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Biomedical subjects

A Butturini

Publications and source records attributed to A Butturini.

At least 19 recordsLinked to original sources
PubMed1997

How important is hepatitis C virus (HCV)-infection in persons with acute leukemia?

Hepatitis C virus (HCV)-infection is common in persons with leukemia. Blood transfusions are the typical source and HCV-related chronic hepatitis a common outcome. Development of HCV-infection and -related hepatitis raises important questions about subsequent leukemia treatment including the natural history of the infection and need for treatment modification. Although the natural history of HCV-infection and -related hepatitis in this setting is unknown, data from normal persons with HCV-infection suggest that short-term survival is not likely to be decreased in persons with leukemia and these complications. In contrast, long-term survival may decrease because of a high rate of chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma. There are no convincing data that HCV-infection or -related hepatitis or alterations in anti-leukemia drug dose or schedule prompted by abnormal liver function tests, alter leukemia outcome. Consequently, it is uncertain whether drug doses and/or schedule should be modified in persons with leukemia and HCV-infection or -related hepatitis. Short-term outcome of blood cell and bone marrow transplants is also unaffected by HCV-infection or -related hepatitis.

Acute Disease↗
PubMed1996

BCR/ABL and leukemia.

This review focuses on the role of the chimeric BCR/ABL gene in leukemia development. First, we discuss and update knowledge regarding the molecular biology of BCR/ABL. We then review data regarding transforming activity of BCR/ABL. Third, we discuss the complex interactions between BCR/ABL and leukemia phenotype. We conclude with a brief discussion of possible therapeutic implications of these data.

Animals↗
PubMed1995

Bone marrow transplantation for Fanconi anemia.

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Adolescent↗
PubMed1995

Concepts underlying autotransplants for cancer.

In this brief review we consider concepts that underlie use of autotransplants to treat cancer including whether more intensive chemotherapy is better, whether an autotransplant is needed, whether the benefit of more intensive chemotherapy exceeds the risk of causing relapse with the graft, whether blood or bone marrow autotransplants are better and whether immune-mediated anti-cancer effects operate after autotransplants.

Combined Modality Therapy↗
PubMed1994

Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study.

We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.

Adolescent↗
PubMed1994

Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure.

Fanconi anemia is an autosomal recessive disease characterized by a high risk of developing bone marrow (BM) failure and acute myelogenous leukemia. We studied growth of hematopoietic progenitor cells in long-term BM culture (LTBMC) in 8 persons with Fanconi anemia and BM failure. Although LTBMC were initiated with very few BM cells, an adherent layer formed in cultures from 7 persons. In these cultures, the number of nonadherent cells increased for 10 to 15 days. Cell growth continued until cultures were terminated at day 35 to 40. During the first 2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By days 35 to 40, the adherent layer contained cells able to initiate secondary LTBMCs. These data indicate that hematopoietic precursors cells able to proliferate and differentiate in vitro are present in the BM of persons with Fanconi anemia and BM failure. They suggest that mechanisms other than absent precursor cells are responsible for BM failure in Fanconi anemia.

Adolescent↗
PubMed1994

Hematopoietic recovery after 10-Gy acute total body radiation.

Considerable data suggest that very high doses of acute total body radiation destroy most hematopoietic stem cells and that recovery is possible only after a bone marrow transplant. We review data from a radiation accident victim exposed to about 10-Gy or more acute total body radiation. Total dose and uniformity of distribution were confirmed by physical measurements (paramagnetic resonance), computer simulation, and biologic dosimetry (granulocyte kinetics and cytogenetic abnormalities). Treatment consisted of supportive measures, transfusions, and hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor and interleukin-3). Hematopoietic recovery occurred slowly. Granulocytes were detectable throughout the postexposure period, exceeding 0.5 x 10(9)/L by day 37. There was slower and incomplete recovery of red blood cells and platelets. Increases in blood cell production were paralleled by morphologic changes in bone marrow biopsies. Gastrointestinal toxicity was moderate. Death from a probable radiation pneumonitis infection occurred on day 130. These data indicate the possibility of hematopoietic recovery after approximately 10 Gy or more acute total body radiation without a transplant. They also suggest that lung rather than gastrointestinal toxicity may be dose-limiting under these circumstances.

Adult↗
PubMed1994

Allogeneic bone marrow transplantation for leukemia.

Allogeneic bone marrow transplantation cures some persons with acute lymphoblastic leukemia, acute myeloblastic leukemia, and chronic myelogenous leukemia. Considerable data suggest that most cures result from immune-mediated antileukemia effects of the transplant rather than intensive pretransplantation chemotherapy and radiation. The mechanism of these immune-mediated effects, termed graft-versus-leukemia, is unknown. In the past 25 years more than 20,000 allogeneic transplantations were performed worldwide in persons with leukemia. Here we review single- and multicenter studies and analyses of the International Bone Marrow Transplant Registry on results of allografts for leukemia.

Antineoplastic Agents↗
PubMed1993

Recent progress in understanding chronic myelogenous leukemia.

Several important issues in CML research are not covered in this brief review such as the structural or molecular basis of the translocation between ABL and BCR, the relationship between CML and ALL with an identical or related BCR/ABL abnormality, the biology of CML stem and progenitor cells and immunologic aspects of CML. These are discussed elsewhere in this volume. The data reviewed indicate considerable progress in understanding the molecular and cell biology of CML. More is known about what causes CML than any human cancer. However, many important unresolved issues are likely to provide a productive direction for future studies.

Animals↗
PubMed1993

Clinical models of autotransplants in chronic myelogenous leukemia.

We analysed relapse risk after syngeneic and allogeneic T cell depleted transplants to predict the outcome after autotransplants in chronic myelogenous leukemia (CML). These data suggest that high dose pre-transplant conditioning may cure about 50% of the persons in chronic phase and about 10% of those in more advanced phases. The expected relapse rate would be about 50-90%. However, additional relapses might occur from infusing leukemia cells with the graft. Different approaches are being attempted to eliminate leukemia cells from the graft. It is however unlikely that their effect could be demonstrated in clinical trials. Recent analyses in persons relapsing after allogeneic T depleted transplants suggest that reducing the CML cell mass by high dose chemotherapy may prolong duration of survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Radiation accidents: primum non nocere.

BM toxicity is a major cause of morbidity and mortality after exposure to acute high dose total body radiation. Here, we consider therapeutic strategies useful in victims of radiation accidents including supportive care (antibiotics, protected environments and transfusions), hematopoietic growth factors and BMTs. Selecting the best strategy requires precise knowledge of the details of radiation exposure. This information is rarely available in accidents. An alternative is to assess risk:benefit ratios for different strategies at approximate radiation doses. Using this approach, we suggest supportive care be given to all persons at risk of developing BM failure. The favorable risk:benefit ratio of hematopoietic growth factors argues for their use when moderate to severe BM failure is predicted. Transplants, which have the least favorable risk:benefit ratio, should be used only when there is a substantial risk of irreversible BM damage.

Bone Marrow↗
PubMed1992

Survival of children with chronic myeloid leukemia.

We analyzed survival in 203 children with Philadelphia-chromosome-positive chronic myeloid leukemia (CML). Median survival was 4.1 years; average annual risk of death was 20%. These survival data are similar to those reported in adults. Because there is no possibility of long-term disease-free survival in children with CML with conventional therapies, the findings of this study suggest that bone marrow transplantation should be considered in these patients.

Adolescent↗