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Biomedical subjects

A Butturini

Publications and source records attributed to A Butturini.

At least 55 records · Page 3Linked to original sources
PubMed1991

[Autotransplants in leukemia: current status and perspectives].

Autotransplants in leukemia are controversial; their rationale and results have been questioned. Here we consider several issues central to this debate: (1) Are there convincing data that more intensive therapy increases cures; (2) Are results post autotransplant a consequence of the transplant or do they reflect subject-selection and time-to-treatment (time censoring) biases; (3) Does leukemia relapse after autotransplant develops from persisting leukemia cells in the subject or the graft; (4) Do autotransplants using hemopoietic stem cells from different sources have distinct outcomes; (5) Are immune mediated anti-leukemia mechanisms likely to prevent relapse after autotransplants; and (6) Can comparably intensive therapy be given without an autotransplant.

Forecasting↗
PubMed1991

[Stem cells, clonality and leukemia].

The data we review suggest newer concepts regarding the biology of leukemia. First, all leukemias may originate in a multipotent stem cells. Second, leukemia phenotype may reflect where the leukemia clone expands rather than the site of transformation. Third, preleukemia may always antedate leukemia. And finally, remission and cure may result from re-establishing preleukemia rather than eradicating leukemia cells of favoring their maturation. Also, leukemia and at least some cases of aplastic anemia may represent different ends of a spectrum of one disease.

Clone Cells↗
PubMed1990

Autotransplants in chronic myelogenous leukaemia: strategies and results.

Autotransplants are increasingly used in chronic myelogenous leukaemia (CML). Most are performed in advanced leukaemia; now, autotransplants in chronic phase are being evaluated. Treatment involves high-dose chemotherapy with or without radiation followed by a transplant of previously cryopreserved stem cells derived from bone marrow or blood. The transplanted bone marrow may be manipulated in vitro to remove CML cells. Results vary. Transplants in advanced CML usually re-establish chronic phase but responses are brief. After transplants in chronic phase some recipients become Philadelphia chromosome negative for a year or more; others remain Ph-chromosome positive. There are insufficient data to show whether these early transplants prolong chronic phase duration or increase survival. The incurability of CML by conventional therapy should encourage further studies of this approach.

Actuarial Analysis↗
PubMed1990

Treatment strategies for acute lymphoblastic leukemia.

We analyzed LFS in adults, adolescents, and children with ALL treated by using different therapies and therapeutic strategies. In most instances, the strategy of initial chemotherapy followed by transplantation in those who relapse produced the highest LFS. Results of HLA-identical transplants were generally superior to those of autotransplants. However, many persons do not have donors and should be considered for autotransplants or possibly for transplants from partially or fully HLA-matched related or unrelated donors. These persons are also potential candidates for evolving therapeutic strategies such as immune therapy or lymphoid growth factors.

Adolescent↗
PubMed1990

GM-CSF incubation prior to treatment with cytarabine or doxorubicin enhances drug activity against AML cells in vitro: a model for leukemia chemotherapy.

We studied the effect of preincubation with recombinant GM-CSF on the activity of cytarabine and doxorubicin against clonogenic acute myeloid leukemia cells (CFU-AML). Leukemia cells from seven persons with AML, three myeloid cell lines (HL60, KG1, K562) and two control cell lines (U937, MOLT3) were tested. Preincubation with GM-CSF (0.01-0.1 microgram/ml) increased DNA synthesis as measured by tritiated thymidine incorporation and intranuclear Ki67 expression in cells from six persons with AML and in HL60 cells. Leukemia cells preincubated with GM-CSF for 6-48 h were exposed to cytarabine (2-200 micrograms/ml) or doxorubicin (0.01-0.1 microgram/ml) for 3 h and CFU-AML assayed. This approach further reduced CFU-AML in samples from six persons with AML and in HL60 and KG1 cells compared to cells not preincubated with GM-CSF prior to drug treatment. In most instances, reduced CFU-AML correlated with GM-CSF induced DNA synthesis. These data suggest a possible strategy of GM-CSF pretreatment to increase anti-leukemia efficacy of chemotherapy in AML.

Cytarabine↗
PubMed1990

Use of hematopoietic growth factors in radiation accidents.

Molecularly cloned hematopoietic growth factors are likely to be useful in treating radiation victims with bone marrow suppression. Some effects, such as increased granulocytes, are clearly beneficial. Other effects, such as altering the probability of survival of hematopoietic stem cells, may also be important. Interesting questions remain to be studied including which molecularly cloned hematopoietic growth factor(s) to use, optimal dose, timing, combinations of growth factors, and other issues. Some can be studied in vitro or in animal models. Others require clinical trials. Molecularly cloned hematopoietic growth factors clearly herald a new era in treating radiation accidents.

Accidents↗
PubMed1990

Transplants of blood-derived hematopoietic cells.

Increasing numbers of transplants, particularly autotransplants, are performed using blood-derived cells. Most subjects have leukemia but others have solid tumors or even genetic disorders. Despite this expanding data base, several important issues are unresolved. Can blood-derived cells reconstitute short-term hematopoiesis? Here, the answer is likely yes, although this is not yet proven. Studies using genetically marked cells should resolve this issue. Next, can blood-derived cells reconstitute long-term hematopoiesis? Here, the answer is unknown, but it would not be surprising were this not so. However, since most (if not all) high-dose chemotherapy and radiation treatments do not completely eradicate endogenous hematopoietic stem cells, reconstitution of long-term hematopoiesis from the graft may not be necessary for blood-derived grafts to be useful clinically. Another unresolved area is whether blood-derived grafts have a lower likelihood of tumor recurrence because of a lower probability of tumor contamination (qualitative or quantitative) or because of a different cellular composition of the graft. This issue is only answerable in controlled trials. Most data suggest that recurrence rate would not be higher than bone marrow-derived grafts. Whether it is lower is unknown. Analysis of this point is confounded by the fact that most (perhaps all) relapses that occur post-transplant using current conditioning schedules are explicable by residual leukemia in the recipient. Thus, tumor contamination of the graft is not presently an operationally important issue. There are some recent developments in this area. One is the use of umbilical cord blood cells to reconstitute hematopoiesis in a child with Fanconi anemia. Additional data are needed to evaluate this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗
PubMed1990

The role of hematopoietic growth factors in nuclear and radiation accidents.

Molecularly cloned hematopoietic growth factors are likely to be useful in treating persons with bone marrow failure resulting from radiation exposure. Some effects, such as increased granulocytes or platelets, are of clear therapeutic benefit. Other effects, such as a direct action on survival of hematopoietic stem cells and improved granulocyte function, may also increase survival. Many important areas remain to be studied, including which molecularly cloned hematopoietic growth factor(s) to use, optimal dose and timing, and others. Some of these issues can be studied in clinical trials; others require in vitro or animal models. Despite the limited data currently available, it is clear that the availability of molecularly cloned hematopoietic growth factors heralds a new era in treating radiation and nuclear accidents.

Accidents↗
PubMed1990

Oncogenes and leukemia.

Cellular or proto-oncogenes are normal cellular genes important in normal cell growth and development. In some instances abnormal expression of these genes is associated with altered cell growth or with malignant transformation. Abnormalities of cellular oncogenes are common in human leukemias. These arise by multiple mechanisms such as mutation, translocation, amplification, and others. Sometimes more than one abnormality is present within a single oncogene. In other instances, a leukemia cell may contain abnormalities of several different oncogenes. Some oncogene abnormalities are relatively specific for certain leukemias and occur in almost all cases; examples include ABL in chronic myelogenous leukemia or MYC in Burkitt leukemia/lymphoma. Other abnormalities are also relatively specific but occur in only some cases such as NRAS in acute myelogenous leukemia or BCL2 in B-cell acute lymphoblastic leukemia. In other leukemias, such as most cases of acute lymphoblastic leukemia and chronic lymphocytic leukemia, oncogene abnormalities are uncommon. The precise role of oncogenes in the pathogenesis of human leukemia is unknown. Retrovirus transduced versions of some of the oncogenes modified in human leukemias cause leukemia in animals. Other oncogenes, modified or unmodified, transform animal and human hematopoietic cells in vitro. Some oncogene products are hematopoietic growth factors or growth factor receptors while others regulate cell proliferation or differentiation by diverse mechanisms. Disruption of the balance between these processes seems the most likely mechanism of oncogene related leukemogenesis. If the role of oncogenes in human leukemias can be defined, innovative diagnostic and therapeutic strategies may be forthcoming.

Animals↗