Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous bone marrow transplantation (ABMT) for chronic myelogenous leukemia (CML) is limited because of the difficulty in purging Ph chromosome positive cells from bone marrow cells (or peripheral blood stem cells). Combining hyperthermia with certain drugs that affect Ph+ cell growth in vivo and in vitro may enhance the killing (apoptosis) of CML cells in vitro. In this study, we chose such drugs (i.e., azidothymidine [AZT], interferon-alpha [IFN-alpha], tumor necrosis factor [TNF], and quercetin) and tested this hypothesis using two CML-derived cell lines in vitro, K562 and KU812, to enhance the killing of CML cells with heat. Our results indicate that the optimal hyperthermic purging effect is achieved by heating at 42 degrees C for 1 hour with IFN-alpha (100 U/mL) and AZT (0.5 microM/L) or with quercetin (50 microM) [corrected], depending on the sensitivity of the CML cells eliminated in vitro. K562 cells were significantly eradicated by a combination of IFN-alpha and AZT, while KU812 cells were significantly inhibited by quercetin at the temperature and drug concentrations above. This combined effect may enhance apoptosis of CML cells in vitro.
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PMID:Enhanced elimination of Ph+ chromosome cells in vitro by combined hyperthermia and other drugs (AZT, IFN-alpha, TNF, and quercetin): its application to autologous bone marrow transplantation for CML. 772 Aug 16

Sweet's syndrome with malignancy or acute neutrophilic dermatosis (AND) is an unusual cutaneous disorder seen most commonly in association with acute myelogenous leukemia. A large majority of patients with AND and malignancy have neoplasms of hematopoietic, plasma cell or lymphoid nature. The patient reported here had myelofibrosis, chronic myelogenous leukemia and Sweet's syndrome. The individual lesions responded to intralesional interferon-alpha 2, which has not to our knowledge been reported previously. This result, however, was not as great as the response of AND to intralesional steroid injections.
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PMID:Sweet's syndrome with myelofibrosis and leukemia: partial response to interferon. 772 40

Two hundred and nineteen cases of Ph+ve CML and 15 Ph-ve, BCR+ve CML cases have been analysed to determine the breakpoint site and its relationship to clinical features, cytogenetic response, duration of chronic phase and survival. 119 cases have had RNA analysis performed to determine the type of BCR/ABL transcript and have also been analysed in a similar way. Presenting features at diagnosis including age, sex, white-cell count and platelet count showed no significant difference for those with 5' and 3' breakpoints and those with either b2a2 or b3a2 BCR/ABL transcripts. However, in a subgroup of patients whose presenting white-cell count was < 100 x 10(9)/l, those with b3a2 transcript did have a significantly higher platelet count. Analysis by Sokal risk grouping showed no difference for 5' or 3' breakpoints but a trend for lower stage among those with b2a2 transcripts. No correlation was found either for genomic breakpoint site or BCR/ABL RNA transcript in terms of duration of chronic phase or survival. When stratified by randomized therapy, either interferon-alpha or standard chemotherapy, no difference was noted in relation to genomic breakpoint site or BCR/ABL transcript. Cytogenetic response was not related to the molecular findings.
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PMID:Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival. 773 53

To assess the influence of pretransplant cytoreductive therapy with special reference to interferon-alpha (IFN-alpha) treatment on major endpoints of allogeneic bone marrow transplantation (BMT), we studied 133 consecutive patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in first chronic phase who received marrow grafts from HLA-identical family (n = 103) or alternative donors (n = 30) at a referral-based transplant center. Fifty of these patients (38%) were previously exposed to IFN-alpha for a median duration of 14 months (range, 1 to 61 months), whereas 83 patients (62%) exclusively received hydroxyurea and/or busulfan therapy between 1 and 129 months (median, 15 months) pretransplant. Using the categorized treatment duration with each pretransplant cytoreductive agent as a measure for individual patient exposure to each agent, prolonged ( > 12 months) IFN-alpha administration was identified as the sole significant pretransplant therapy-related predictor of transplant outcome by proportional hazards regression analysis. The adjusted risk ratio (RR) of transplant-related mortality (TRM) was 2.5-fold higher (95% confidence limits [95% CL], 1.4 to 4.5; P < .004) compared with other pretransplant therapy and this was mainly attributable to a 3.1-fold higher RR (95% CL, 1.4 to 6.4; P < .005) of fatal posttransplant infections after prolonged IFN-alpha treatment pretransplant. Marrow graft failure developed exclusively among 7 of 30 patients (23%) with donors other than HLA-identical family members and was further restricted to patients who had been previously exposed to IFN-alpha. The probability of graft failure was 49% +/- 28% in 17 patients pretreated with IFN-alpha compared with 0% for the other 13 patients with mismatched family or unrelated donors (P < .008). In addition, a significant delay in neutrophil and platelet count reconstitution was observed among patients with donors other than HLA-identical family members after pretransplant IFN-alpha exposure. No influence of pretransplant cytoreductive therapy on either acute and chronic graft-versus-host disease or leukemic relapse was detected in this study. As a consequence of its adverse effect on TRM, prolonged pretransplant IFN-alpha treatment was independently associated with a 2.5-fold lower likelihood (95% CL, 1.4 to 4.5; P < .003) of 5-year overall survival and with a 2.3-fold lower likelihood (95% CL, 1.3 to 4.2; P < .004) of 5-year disease-free survival postransplant after adjustment for other significant prognostic factors in multivariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prolonged administration of interferon-alpha in patients with chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia before allogeneic bone marrow transplantation may adversely affect transplant outcome. 774 58

Interferon-alpha may be better than cytotoxic drugs in the long-term management of patients with chronic myeloid leukaemia (CML) in chronic phase. To test this possibility 587 patients with CML in chronic phase were randomly allocated to receive lymphoblastoid cell-line interferon-alpha n1 (IFN-alpha, n = 293) or chemotherapy with busulphan or hydroxyurea (no IFN-alpha, n = 294) as maintenance after initial induction treatment with cytotoxic drugs. There was a significant survival benefit for patients in the IFN-alpha arm when analysed on the basis of intention to treat (2p = 0.0009). The median survival for those allocated IFN-alpha was 61 months and no IFN-alpha was 41 months. Out of 269 patients with Philadelphia-positive CML in the IFN-alpha arm with at least 6 months follow-up, 211 were evaluable for haematological response: 145 (68%) achieved good responses (A+ or A type), 37 (18%) had partial responses (B type) and 29 (14%) had poor responses (C type). Patients with types A and B responses had a better survival than those in the no IFN-alpha arm; patients with type C responses had survival equivalent to the no IFN-alpha arm. Of these 269 patients, 26 of whom had not started IFN-alpha, 59 (22%) achieved a significant degree of cytogenetic response but 210 (78%) did not have a response. Cytogenetic responders survived significantly longer than non-responders and even non-responders survived longer than patients in the no IFN-alpha arm. Since cytogenetic non-responders had worse than average prognostic features, they may also benefit from IFN-alpha therapy. We conclude that treatment with IFN-alpha prolongs the survival of patients with CML; benefits of IFN-alpha are not confined to cytogenetic responders but may extend to most, if not all patients receiving IFN-alpha treatment; and cytogenetic response to IFN-alpha treatment identifies patients with a relatively good prognosis.
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PMID:UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. 776 Jun 9

A 13 year old girl diagnosed as having chronic myeloid leukemia (CML) was treated with interferon-alpha (IFN-alpha) alone and 4 months later hematological remission was obtained. In the course of the IFN-alpha treatment there was neither infectious sign nor side effects. In this study we have examined the effect of IFN-alpha on superoxide O2- generation by polymorphonuclear neutrophils (PMN). The PMN of the patient generated less O2- than PMN from normal controls. When patient PMN were cultured in the presence of 1000 U/mL IFN-alpha, enhancement of the formyl-methionyl-leucyl-phenylalanine induced O2- generation following priming with tissue necrosis factor-alpha was observed. Over the course of the IFN-alpha therapy, such O2- generation was gradually restored. It is suggested that CML PMN are in the resting condition in terms of their ability to generate O2- and that IFN-alpha is effective in inducing O2- generation by CML PMN.
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PMID:Interferon-alpha potentiates priming-dependent FMLP-induced neutrophil superoxide generation in a patient with chronic myeloid leukemia. 779 60

Metaphase DNA fluorescence in situ hybridization (metaphase-FISH) was performed on follow-up samples from 60 patients suffering from haemopoietic malignancies (acute and chronic myeloid leukaemia, acute lymphoblastic leukaemia, non-Hodgkin's lymphoma and myelodysplastic syndrome). All patients had clonal chromosomal trisomies or translocations at diagnosis, and were treated by bone marrow transplantation (BMT), chemotherapy (CT) or interferon-alpha therapy. Metaphase-FISH was performed during therapy-induced complete haematological remission (CR) (BMT and CT patients) using biotin-labelled whole chromosome paint probes. 28% of all patients in CR were shown by FISH to have abnormal metaphase cells, and 62% of this group suffered a clinical relapse. Of those with negative FISH results (72%), 12% relapsed. In three CML patients treated with BMT a small population of t(9;22)-positive cells was demonstrated. These cells disappeared during follow-up without causing a relapse. One ALL patient had abnormal cells a short time after start of therapy but was also later found FISH-negative. Furthermore, we demonstrated that metaphase-FISH is a suitable method for quantifying the proportion of abnormal cells in CML patients during interferon-alpha therapy. Metaphase-FISH was also employed to detect a local relapse in an ALL patient. Thus, metaphase-FISH was found reliable and sensitive for detection of minimal residual disease in patients with haemopoietic malignancies.
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PMID:Metaphase fluorescence in situ hybridization (FISH) in the follow-up of 60 patients with haemopoietic malignancies. 781 2

A 46-year-old man with chronic myelogenous leukemia (CML) was admitted to our hospital because of high fever. The chest radiographs showed bilateral groundglass-like infiltrates in the perihilar region. Transbronchial lung biopsy (TBLB) and autopsy revealed PAS-positive granular materials characteristic of pulmonary alveolar proteinosis (PAP). He had received interferon-alpha since the time of CML diagnosis. Busulfan had never been administered. Altered cell-mediated immunity was thought to be closely related to the development of PAP.
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PMID:Rapidly progressive pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia. 784 88

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.
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PMID:Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. 785 36

The combination of donor leucocytes, with or without interferon, has produced encouraging responses in patients with haematological relapse following allogeneic BMT for chronic myeloid leukaemia (CML). A 25-year-old male received low-dose interferon-alpha alone for haematological relapse occurring 10 months following an allogeneic BMT for Ph-positive CML. Interferon therapy was complicated by severe GVHD requiring immunosuppressive therapy. The patient was subsequently found to be in complete haematological and cytogenetic remission, raising the possibility of an immune-mediated antileukaemic action.
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PMID:Graft-versus-host disease following interferon therapy for relapsed chronic myeloid leukaemia post-allogeneic bone marrow transplantation. 785 42


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