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Biomedical subjects

G Gahrton

Publications and source records attributed to G Gahrton.

At least 19 recordsLinked to original sources
PubMed1992

Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia.

Approximately 10% of B-cell chronic lymphocyte leukemia (B-CLL) cases have structural chromosomal aberrations involving band 13q14. To evaluate a possible role of RBl gene deletions in B-CLL we investigated the malignant cells of 27 patients by molecular genetic and cytogenetic techniques. Four of the cases had chromosomal aberrations that involved 13q14 (including one case with a 13q14 deletion that was observed in a single metaphase cell), and 11 had other chromosomal abnormalities, whereas the malignant cells of 12 patients were either cytogenetically normal or failed to divided in vitro. Eight patients (30%) were found to have hemizygous deletions of the RBl gene. These cases included all four patients with chromosomal changes at 13q14, but also three patients without chromosome abnormalities and one case with a chromosomal aberration not involving 13q. The deletions were interstitial in all cases but one, as defined by probes located centromeric and telomeric of the RBl locus. Inactivation of RBl may thus be a significant event in the development of some B-CLL clones.

Autoradiography↗
PubMed1992

A predictive model for the clinical response to low dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia.

The response to treatment with low-dose ara-C was studied in 102 consecutive patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo-Pelger morphology and > or = 2 chromosomal aberrations. Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38.6% of the patients, with a response rate of > 50%, an intermediate group, 32.7% of the patients, with a response rate of 24%, and an unfavourable group, 28.7% of the patients, with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two-thirds of patients with MDS and MDS-AML by identifying patients who should not be treated with low-dose ara-C as well as patients with a relatively high probability of response.

Aged↗
PubMed1992

Bone marrow transplantation for acute non-lymphoblastic leukemia.

Most results obtained by different study and analytic designs favor that matched allogeneic BMT is superior to chemotherapy in young adults with ANLL in first remission. The place of ABMT is more difficult to assess and requires further study both compared to chemotherapy and allogeneic BMT. Furthermore, the question of purging needs further study in a controlled fashion. For older patients the choice is more difficult. Transplant related mortality increases with age which makes ABMT an attractive alternative to allogenic BMT. However, recent advances in prophylaxis and treatment of transplant related complications such as cytomegalovirus interstitial pneumonia and veno-occlusive disease of the liver might increase long-term survival after allogeneic BMT in older patients. The role of matched unrelated donors in the treatment of ANLL is unresolved but this procedure should probably be reserved for relatively young patients in second complete remission or later.

Antineoplastic Agents↗
PubMed1992

No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia: results of a prospective randomized study.

A total of 239 patients with chronic myeloid leukaemia (CML) in chronic phase awaiting bone marrow transplantation (BMT) from an HLA-identical sibling donor were randomized to receive, as part of their conditioning, splenic irradiation (SI+) or no splenic irradiation (SI-). There was no difference between the SI+ and SI- groups regarding the distribution of age, sex, donor/recipient sex combination and blood counts at diagnosis and at BMT. Survival, leukaemia-free survival (LFS), incidence of transplant-related mortality, incidence of rejection and probability of relapse do not differ between the 117 SI+ and the 118 SI- patients at a median follow-up time of 2.5 years (minimum 0.5 years). LFS at 30 months is 56% (SE 5%) for the SI+ and 51% (SE 6%) for the SI- group (p = 0.65). LFS is better for younger patients (less than 25 years), for patients without T cell depletion and for those with a low white blood cell count at diagnosis (less than 30 x 10(9)/l) (p less than 0.05). It is worst for male recipients of a female marrow (p less than 0.05). The incidence of graft-versus-host disease grade greater than or equal to II was higher in the SI+ group, though not significantly. We conclude that routine splenic irradiation prior to BMT for patients with CML is of no benefit and should not be used as a routine procedure.

Adolescent↗
PubMed1991

Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation.

BACKGROUND AND METHODS: In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. RESULTS: At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remission after engraftment. There were trends toward longer survival among patients who were responsive to treatment before bone marrow transplantation, patients with Stage I disease at diagnosis, and patients who had received only first-line treatment before transplantation, as compared with those who were not responsive, those with Stage II or III disease at diagnosis, and those who had received three or more lines of treatment, but the differences in these factors were not statistically significant. Two post-transplantation factors predicted better long-term survival: complete remission after engraftment and grade I graft-versus-host disease, rather than grade II, III, or IV. CONCLUSIONS: Allogeneic bone marrow transplantation with the use of HLA-matched sibling donors appears to be a promising method of treatment for some patients with multiple myeloma.

Adult↗
PubMed1991

Treatment of multiple myeloma with interferon alpha: the Scandinavian experience.

IFN alpha is a biologic therapeutic agent with documented antitumoral effect in multiple myeloma. 15% of previously untreated myeloma patients achieve a clinical response to IFN alpha alone with a possible dose-response relationship. A particularly good effect is noted in IgA myelomas treated with natural IFN alpha. A randomized study was started in April 1986 comparing melphalan/prednisone (MP) therapy with MP plus natural IFN alpha (MP/IFN) in untreated patients with multiple myeloma stages II and III. 220 patients had entered the study by autumn 1989. An interim report is given here. The response frequency was 48% in the MP group and 66% in the MP/IFN group (P less than 0.02). Stage II patients responded better to MP/IFN (76%) than to MP alone (48%) (P less than 0.01). No significant difference was noted for stage III patients. 91% of all IgA myelomas responded to MP/IFN and 52% to MP (P less than 0.01). The difference in response frequency of IgG and BJ myelomas between the two treatment groups was not statistically significant. The observation period is still too short to draw firm conclusions on survival. However, a statistically significant longer response duration time and survival from response (P less than 0.01) was noted for stage II patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Acute leukemia in professional drivers exposed to gasoline and diesel.

The environmental exposure to the petroleum products gasoline, diesel, and their motor exhausts was studied in a case-control interview of 125 patients with acute leukemia and 1 matched control per patient. Odds ratios were calculated by comparing discordant matched patient-control pairs. An excess risk for developing acute leukemia was found for the professional drivers, and odds ratio was determined to be 3.0 (95% CI: 1.1-9.2/p less than or equal to 0.02). For those who were exposed for more than 5 years in their life-time, or more than 1 yr during the 5-20 yr period prior to diagnosis, the odds ratio was 5.0 (p less than 0.05). This finding remains after consideration is given to exposures to organic solvents, smoking and therapeutic x-ray treatment. No excess risk was observed for persons professionally exposed to motor oil and machine oil without exposure to fuels and exhausts. No preferential type of acute leukemia was found to be associated with exposure to fuels and their exhausts. The results indicate an etiological relationship between the development of acute leukemia and exposure to petroleum products as fuels and exhaust.

Acute Disease↗
PubMed1991

Methotrexate combined with cyclosporin A decreases graft-versus-host disease, but increases leukemic relapse compared to monotherapy.

Forty patients with leukemia receiving HLA-identical sibling marrow and treated with four doses of methotrexate (MTX) in combination with cyclosporin A (CSA) for prevention of graft-versus-host disease (GVHD) were compared with retrospective controls consisting of 57 patients treated with MTX alone and 30 patients treated with CSA alone. Follow-up time ranged from 2.6 to 6.7 years after bone marrow transplantation. Patients in the MTX + CSA group were older and received a smaller marrow cell dose, but were otherwise comparable regarding disease status, donor/recipient sex match and seropositivity for cytomegalovirus (CMV) and other herpes viruses. Engraftment was slowest in the MTX + CSA group and fastest in the CSA group (p = 0.005 vs MTX and p less than 0.001 vs CSA). The incidence of moderate to severe acute GVHD (grade II-IV) was 8% among patients on MTX + CSA and 26% and 47% in the MTX (p = 0.028) and CSA (p = 0.0001) groups respectively. The corresponding figures for chronic GVHD were 25, 42 and 40% (n.s.). The incidence of CMV interstitial pneumonia was 0% in patients treated with MTX + CSA compared to 23% in the MTX treated patients (p = 0.01) and 11% in the CSA treated patients (p = 0.05). The actuarial 3-year survival in the three groups was similar, 56% for the MTX + CSA patients and 53% for both the MTX and CSA patients (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Bone marrow transplantation in multiple myeloma.

Modifications of standard therapy with melphalan and prednisone have not improved the prognosis of patients with multiple myeloma. Encouraging results with high doses of intravenously administered melphalan have generated interest in marrow-ablative therapy with hemopoietic stem cell support. Experience in about 400 patients receiving alkylating agents, sometimes with added total body irradiation, demonstrates partial remissions in virtually all patients with advanced and refractory myeloma, but complete remissions (CR) in less than one-half, even when transplants were performed for responsive disease with low tumor burden. Despite patient and disease heterogeneity, different sources of hemopoietic stem cells (allogeneic or autologous, bone marrow or blood), ex vivo purging of autografts, and different preparative regimens, some general recommendations can be made: (1) Allogeneic BMT should be reserved for patients under age 50, where transplant-related mortality can be expected not to exceed 30%; 40% will achieve CR with a 3-year relapse-free survival expectation of 70%, and (2) With autologous transplantation, low mortality under 10% and marked therapeutic benefit (greater than 30% CR, 80% overall survival at greater than 3 years) seem to be achievable mainly if performed when tumor bulk is low and standard doses of therapy are still effective. Because of the encouraging results even in patients older than 60 years, hemopoietic stem cell grafting should be seriously considered as part of an overall treatment strategy, in order to avoid irreversible normal hemopoietic stem cell damage from nitrosoureas and radiation to marrow-containing bones.

Bone Marrow Transplantation↗