摘要:

Based on population statistics and institutional reviews, the median age of patients developing non-Hodgkin's lymphomas (NHL's) is around 65 years. A review of retrospective studies suggesting that increasing age imparts an adverse prognosis in patients with NHL's is presented. Interpretation of this data is often confounded by referral bias of patients to specialized centres, multiple other NHL-related risk factors and inadequate chemotherapy administration due to age and toxicity related dose reductions. These factors, as well as alterations in tumour-host biology and comorbid diseases which result in changes in pharmacokinetics and pharmacodynamics, are discussed as possible reasons for poorer outcome in the elderly. In an effort to develop better tolerated and thus more effective combination chemotherapy for older patients, a number of prospective single arm and randomized clinicaltrials of novel regimens have been undertaken. Improved rates of disease remission and overall survival appear often to have been achieved at the expense of greater morbidity and mortality. Ongoing attempts to improve the therapeutic index include the application of chronic oral chemotherapy, brief duration intensive therapy and fractionation of standard drug doses as well as incorporation of myelo-preserving haematopoietic growth factors. The possibility of developing flexible,“customized”therapy for elderly patients is discussed.

ISSN:1042-8194    

DOI:10.3109/10428199309145876

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The t[14;18] chromosomal translocation is the most common cytogenetic abnormality found in hematolymphoid malignancies. The t[14;18]fuses thebcl-2gene at 18q21 with the immunoglobulin heavy-chain locus at 14q32, resulting in deregulated expression ofbcl-2and production of high levels of its encoded 26-kD protein in the majority of non-Hodgkin lymphomas. Recent data indicate that somatic point mutations frequently occur in translocatedbcl-2alleles, possibly because of the somatic hypermutation mechanism that is associated with the immunoglobulin gene loci and that normally contributes to antibody diversity. In some cases, these mutations can affect the open reading frame of thebcl-2gene and thereby alter Bcl-2 proteins. Here, we review the currently available data about the incidence, biological effects, and possible clinical importance of somatic mutations within the translocatedbcl-2genes of human lymphomas and leukemias.

ISSN:1042-8194    

DOI:10.3109/10428199309145877

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The management of chronic myeloid leukemia (CML) patients who relapse after allogeneic bone marrow transplantation (BMT) is difficult. Hydroxyurea, alpha interferon, second BMT and leukocytes infusion are various options but none of these approaches is clearly optimal.Hydroxyurea controls the symptoms in most patients without any apparent survival benefit.Alpha interferon (IFN) results in haematological remission in most cases with partial or total Philadelphia negativity in 20–30% of patients. Whether IFN therapy prolongs survival is not yet certain. Second BMT results in successful outcome in about half of the patients, however toxicity to the preparatory regimen, post transplant venocclusive disease and acute graft versus host disease are all major complications. An interval of less than 6 months between the initial and second BMT is generally associated with a poor outcome. Buffy coat infusions from the original donor have resulted in a cytogenetic remission in most patients.Less intensive preparatory regimes, donor buffy coat infusion and the use of biological response modifiers post transplant in order to augment the graft versus leukemia effect in high risk patients may indeed be possible areas of improvement in future studies.

ISSN:1042-8194    

DOI:10.3109/10428199309145878

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Two human homeobox genes, HB9 and HLX, are expressed in hematopoietic progenitors and activated lymphocytes. They are implicated in the proliferation of hematopoietic progenitors in response to growth factors and the differentiation of hematopoietic progenitors to mature cell lineages. RNAs from bone marrow cells of patients with acute myeloid or lymphocytic leukemia have high levels of these two genes while similar RNAs from patients with chronic lymphocytic or myeloid leukemias have nearly normal levels. While the significance of these two genes in leukemogenesis is unknown, they are likely to regulate gene transcription during hematopoiesis and their dysregulation may have dire consequences for hematopoietic cells.

ISSN:1042-8194    

DOI:10.3109/10428199309145879

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cyclosporine and prednisone were administered as graft-versus-host disease (GVHD) prophylaxis to nine patients undergoing marrow transplant from HLA matched, unrelated donors. RhGM-CSF was administered at a dose of 250μ;g/m2daily to all patients. The median day of neutrophil recovery to 500/mm3was Day 16. Four patients developed Grade II acute GVHD and four developed Grade 111 acute GVHD. One patient, who survived only 25 days, did not develop GVHD at all. One patient developed systemic infection within the first 28 days after marrow infusion. Comparison of these data to a prior series of patients undergoing bone marrow transplant (BMT) from unrelated donors who were treated with rhGM-CSF along with methotrexate and cyclosporine for GVHD prophylaxis suggests that rhGM-CSF is well-tolerated, neutrophil recovery may be earlier but the severity of GVHD does not appear reduced. Selection of the GVHD prophylaxis regimen may affect the hematopoietic response to cytokine therapy. Further trials with rhGM-CSF in patients undergoing BMT from unrelated donors are required.

ISSN:1042-8194    

DOI:10.3109/10428199309145880

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effects of rhGM-CSF in vivo on the myeloid clonogenic cells present in 6 AML patients was evaluated. The relative number of clonogenic cells fell in 4 of the 6 patients. The effects of rhGM-CSF on the percentage of clonogenic cells in S phase and the sensitivity of clonogenic cells to cytosine arabinoside varied among the patients. These effects were not related to the effects of rhGM-CSF on the white blood cell count or on the proliferative rate of the leukemia cell population as a whole.

ISSN:1042-8194    

DOI:10.3109/10428199309145881

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25–30 mg/mzfludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol.Eleven out of 46 evaluable patients (24%) responded to the therapy. Seven patients (15%) achieved a complete remission, and four (9%) a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17%. Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.

ISSN:1042-8194    

DOI:10.3109/10428199309145882

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara-C) 500 mg/m2[intermediate dose] or 1000 mg/m2[high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils<0.5×109/1) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p= 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC of CML, strengthening the need for alternate approaches to be defined.

ISSN:1042-8194    

DOI:10.3109/10428199309145883

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effects of interferon-γ(IFN-γ) and/or tumor necrosis factor-a (TNF-α) on the growth of leukemic blast progenitors in 6 acute myeloblastic leukemia (AML) patients, 1 chronic myelocytic leukemia (CML) patient in blast crisis and a granulocyte colony-stimulating factor-(G-CSF-) dependent OCI/AMLla cell line established from an AML patient, were studied. Cells of fresh blood samples and the OCI-AMLla cell line were cultured in methylcellulose media and suspension culture in the presence of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) supplemented as a growth stimulatory factor. Both cytokines suppressed the primary and secondary colony formation in methylcellulose culture of leukemic blast progenitors. The recovery of clonogenic cells in suspension culture was also suppressed by IFN-γand TNF-α. The primary colony formation in methylcellulose reflects the terminal divisions of leukemic blast progenitors, while the secondary colony formation in methylcellulose and the clonogenic cell recovery in suspension have been considered to reflect their self-renewal capacity. Therefore, IFN-γand TNF-αare considered to be effective in suppressing not only the terminal divisions but also self-renewal of leukemic blast progenitors. When both cytokines were added simultaneously to cultures, the suppressive effect of each cytokine was enhanced. The results may suggest the effectiveness of IFN-γand TNF-αin the treatment of leukemia.

ISSN:1042-8194    

DOI:10.3109/10428199309145884

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Surface phenotypes and adhesion activity to human umbilical vein endothelial cells (HUVECs) were studied using leukemic cells from 12 Japanese patients with B-cell chronic lymphoid leukemias including 7 with chronic lymphocytic leukemia (CLL), 1 with prolymphocytic leukemia (PLL), 2 with hairy cell leukemia (HCL) and 2 with HCL variant (HCL-V). CD 13 and CD23 were found to be characteristically positive in CLL, whereas they were not expressed in non-CLL cases except for positivity of CD23 in two such cases. Except for CDl lb, all other leukocyte integrins examined (CDlla, CD11c and CD18) and their ligand (CD54) were highly expressed in non-CLL cases. Adhesion activity of leukemic cells to HUVECs after co-culture with HUVECs was well correlated with the expression of CD11b lb, CD18 and CD54, but showed no predilection for any leukemia subtype. Positivity for CD5, CD21, CD23 and CD13 changed after the co-culture with HUVEC. These results suggest that adhesion activity after co-culture does not correlate with the leukemia subtype and that endothelial cells activate or differentiate leukemic cells.

ISSN:1042-8194    

DOI:10.3109/10428199309145885

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor