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)

An increasing number of diseases may be treated successfully by allogeneic bone marrow transplantation (BMT). Initially used for the treatment of immunodeficiency where a cell series or product is replaced, it has now become routine treatment for many forms of leukemia where the transplant provides the rescue after lethal marrow ablation. Recently, diseases such as thalassemia and other inherited metabolic diseases have also been treated by BMT. Formerly the problems of BMT were mainly concerned with graft versus host disease (GVHD) in HLA-matched transplants with HLA-mismatched ones not being possible as GVHD was usually fatal. Since the development of techniques for T cell removal the incidence of GVHD has greatly diminished. T cell removal has also allowed HLA haploidentical mismatched grafts to be performed successfully for immunodeficiency, but there is still a high graft rejection rate in leukemia. This also occurs to a lesser extent with HLA-matched grafts in leukemia. Furthermore, in certain forms of leukemia, particularly chronic granulocytic leukemia, the relapse rate after T cell-depleted BMT is much higher. Trials of better forms of bone marrow conditioning of the recipient are being attempted in order to prevent graft rejection and leukemia relapse. These include total lymphoid irradiation, heavier irradiation and chemotherapeutic regimens, or the use of in vivo monoclonal antibodies such as CAMPATH 1G or anti-LFA-1 (CD11a). In the future, positive selection of stem cells combined with hemopoietic growth factors may allow engraftment without graft versus host disease. This should become the method of choice for autologous transplantation for malignancy. Two monoclonal antibodies directed against the human progenitor cell antigen 1 (HPCA-1) (CD34) have been used for autologous positive stem cell selection in primates and these cells gave full hemopoietic reconstitution in the animals following lethal total body irradiation.
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PMID:Recent advances in bone marrow transplantation. 256 39

We treated 14 patients with Ph-chromosome-positive chronic myeloid leukaemia still in chronic phase by autografting with blood-derived haemopoietic stem cells. Eleven patients were autografted electively after cytoreductive treatment with busulphan (16 mg/kg) and melphalan (60 mg/m2) and three were autografted after marrow cells from HLA-identical sibling donors had failed to engraft. In 13 patients haemopoiesis recovered; one failed to engraft and died 114 d after autografting. Two other patients became pancytopenic and received further stem cell transfusions at 3 and 40 months respectively after first autografting. One patient entered lymphoid transformation and died 14 months after autografting. Twelve patients survive at a median of 41 months (range 24-53) after autografting. Nine of the survivors have required further chemotherapy after autografting and four of the nine were electively autografted on a second occasion. Three patients surviving after autografting for 28, 43 and 53 months respectively have not required further chemotherapy. In two of these patients haemopoiesis is now predominantly Ph-negative. We conclude that autografting in chronic phase might prolong survival in some cases by reducing the size of the leukaemic stem cell population. The fact that initially successful grafts failed in two patients suggests that blood-derived stem cells may have a finite potential for self-replication.
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PMID:Autografting for patients with chronic myeloid leukaemia in chronic phase: peripheral blood stem cells may have a finite capacity for maintaining haemopoiesis. 257 71

Graft rejection after marrow transplantation is generally thought to be mediated by alloreactive immune effector cells of host origin. Transfused blood products also contain immune cells capable of alloreactivity against both donor graft and host. To reduce the risk of transfusion-associated graft-versus-host disease (GVHD) and graft rejection, standard procedure is to irradiate all blood products with at least 1,500 rad before transfusion. We report a patient with chronic myelogenous leukemia who developed graft rejection and GVHD after receiving a T-cell-depleted transplant from a serologically HLA-A, B, DR/DQ matched and mixed lymphocyte culture (MLC) nonreactive unrelated donor. Cytogenetic analysis of marrow cells collected at the time of graft rejection revealed a PH1-negative female karyotype that was not consistent with donor cells. Use of specific minisatellite DNA probes (YNH 24, H-RAS, and 3' HVR) revealed the exclusive presence of third-party (neither donor nor recipient) restriction-fragment-length polymorphisms (RFLP) in both peripheral blood and marrow. Repeat RFLP analysis 3 days later showed persistence of this unique third-party banding pattern. DNA-based HLA-typing, using polymerase chain reaction (PCR) and oligonucleotide probe hybridization, also showed these cells to be derived from an individual whose HLA-DR type was distinct from donor and recipient. Together, these findings suggested the presence of a proliferating population of transfused cells possessing alloreactivity against both donor graft and host, despite prior irradiation of all blood products with 2,000 rad. Limiting dilution analysis to assess the frequency of irradiated lymphocytes able to respond to mitogen revealed an approximate 5- to 6-log reduction at 1,500 to 2,000 rad as compared with unirradiated controls. These data indicate that a small percentage of lymphocytes can survive irradiation at these doses and suggest that existing blood-product irradiation guidelines may require reassessment, especially in T-cell-depleted transplant recipients.
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PMID:Third-party-mediated graft rejection and graft-versus-host disease after T-cell-depleted bone marrow transplantation, as demonstrated by hypervariable DNA probes and HLA-DR polymorphism. 257 85

Thirty-three patients with Philadelphia positive (Ph+) chronic myeloid leukaemia (CML) treated in chronic phase by bone marrow transplantation (BMT) with T-cell depleted HLA-identical sibling marrow were evaluable for relapse at a median follow up of 41 months (range 16-59 months). Twenty-six (78%) had Ph+ marrow metaphases demonstrated at some time post BMT. The subsequent pattern of disease was variable. In 15 of these cases haematological relapse occurred within 24 months of BMT. Four patients proceeded to haematological relapse more slowly. Seven patients had only cytogenetic evidence of relapse. Of the 19 patients with haematological relapse, five received second transplants and two survive; 13 of the other 14 survive in chronic phase at median times from allografting and from recognition of haematological relapse of 41 months (range 25-59 months) and 18 months (range 5-36 months) respectively. For these 13 patients disease progression after relapse seems to be relatively indolent. In the four patients we could study, blood lymphocytes were almost all of donor origin. We suggest that even in patients with cytogenetic or haematological evidence of relapse after T-cell depleted BMT, leukaemic cell proliferation may still be restrained to some extent by a graft-versus-leukaemia effect mediated by donor-derived lymphoid cells.
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PMID:Slow evolution of chronic myeloid leukaemia relapsing after BMT with T-cell depleted donor marrow. 261 Nov 34

These data indicate that the increment in the anti-leukemia effect, as expressed as FFR, is comparable for transplants for AML in first remission, advanced leukemia, and in persons never achieving remission. These data are consistent with the notion that the major anti-leukemia effect of HLA-identical bone marrow transplantation in AML results from an immune-mediated graft-versus-leukemia effect rather than from high doses of chemotherapy and radiation. Of course, other factors might explain these results. The superior outcome observed for transplants in first remission versus more advanced disease results not from increased anti-leukemia efficacy of transplants but rather that more persons already cured by chemotherapy receive transplants. Otherwise stated, a substantial portion of the persons cured following transplantation for AML in first remission were cured before receiving a transplant. These data have implications for other aspects of bone marrow transplantation. For example, it is suggested that transplants should be performed earlier in solid tumors when these diseases are more likely to respond to high-dose chemotherapy and radiation. Although this hypothesis may be correct, it need not necessarily be so as evidenced by these data in AML. The data we review show that bone marrow transplants in AML are of comparable anti-leukemia efficacy when performed in first remission, advanced leukemia, and initial resistant disease. Similar conclusions may apply to transplants in CML and ALL. The superior overall outcome observed with transplants in earlier leukemia results from transplanting a greater proportion of subjects already cured by chemotherapy. The increased anti-leukemia efficacy of transplants when compared with chemotherapy is compatible with an anti-leukemia effect other than that of high-dose chemotherapy and radiation. An immune-mediated graft-versus-leukemia effect is a likely explanation. Caution in predicting results of autotransplants in solid tumors is likewise necessary.
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PMID:Is transplantation in first remission AML more effective than in advanced leukemia? 261 62

Chronic myeloid leukaemia, a clonal myeloproliferative disorder with a biphasic nature, is characterised by a specific chromosomal aberration, the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a reciprocal translocation between chromosomes 9 and 22 and involves the ABL and BCR genes resulting in a chimeric mRNA encoding a specific protein, termed P210. At present, there is no convincing evidence that to maintain the leucocyte count within the normal range prolongs the duration of the stable chronic phase or of survival, and the objectives of treatment are simply to alleviate symptoms or to delay their onset. It has, however, become clear that bone marrow transplantation performed during the chronic phase using an HLA-identical sibling donor offers the best chance of a cure.
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PMID:Chronic leukaemias: can they be cured? Part 1: Chronic myeloid leukaemia. 262 42

Because the majority of patients with chronic myeloid leukaemia (CML) lack HLA identical siblings, attention has turned in recent years to the possibility of using suitably matched unrelated donors. Tissue typing methods must be refined to help identify the closest possible HLA phenotypic identity. For donor recipient matching the use of the mixed lymphocyte reaction is generally unhelpful and methods that predict for the incidence and severity of graft-versus-host disease, such as assay of cytotoxic T-lymphocyte precursors, may prove especially valuable. Preliminary results from several centres suggest that the probability of survival at two years for patients with CML allografted in chronic phase with matched unrelated donors is 35-40%.
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PMID:Bone marrow transplantation for chronic myeloid leukaemia using matched unrelated donors. 262 22

An analysis of the rate of leukocyte reconstitution in 164 recipients of HLA-identical sibling marrow transplants showed two factors to be independently influential. These were the underlying diagnosis and the type of prophylactic regimen used to minimize the risk of graft-versus-host disease. Patients with severe aplastic anemia had a faster rate of reconstitution of the total white blood cell count to levels of both 500 and 1000 x 10(6)/l than patients with acute non-lymphoblastic leukemia (ANL), acute lymphoblastic leukemia (ALL) or chronic myeloid leukemia (CML). Patients with severe aplastic anemia (SAA), however, did not show a faster rate of reconstitution of blood neutrophils. As well as being slower than patients with SAA for total leukocyte reconstitution, patients with CML were slower than patients with ANL and ALL in attaining a neutrophil count of 500 x 10(6)/l, and slower than patients with ANL in attaining a neutrophil count of 1000 x 10(6)/l. Patients given cyclosporin as the sole immunosuppressant prophylactic regimen post-transplant had faster reconstitution to total leukocyte counts of 500 and 1000 x 10(6)/l and to neutrophils of 1000 x 10(6)/l than patients given methotrexate alone, methotrexate and cyclosporin, or cyclosporin and T cell depletion of the donor marrow. No other factors (including the pretransplant preparative regimen) were significant in influencing the rate of leukocyte or neutrophil reconstitution. When only patients given cyclosporin were analysed, those with severe aplastic anemia continued to show a faster rate of leukocyte reconstitution to WBC 500 x 10(6)/l compared to patients with ANL, ALL or CML, and a faster rate to WBC 1000 x 10(6)/l than patients with CML.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recipients of HLA-identical sibling marrow transplants with severe aplastic anemia engraft more quickly, and those with chronic myeloid leukemia more slowly, than those with acute leukemia. 264 83

Between August 1985 and October 1987 we treated 35 patients with chronic myeloid leukaemia (CML) by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n = 31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n = 35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. The addition of TLI to the standard protocol did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. We conclude that the addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This benefit is not associated with significantly increased toxicity.
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PMID:Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia. 264 59

Monosomy 7 variant childhood chronic myelogenous leukemia (CML) is a rare, fatal leukemia that usually terminates in blast crisis. We report successful marrow transplantation in a patient with this disease using his one HLA locus mismatched mother. Initially following transplant the patient exhibited mixed hematopoietic chimerism, cytogenetic relapse, and clinical relapse of leukemia. However, following recovery from a period of hydroxyurea-induced aplasia, marrow studies showed elimination of the mixed chimerism, absence of the 45,XY,-7 leukemic clone and full engraftment with donor marrow (46,XX). The ability of hydroxyurea to eliminate mixed chimerism in favor of donor hematopoiesis and to eliminate the persistent leukemic clone in this patient with CML suggests treatment approaches worthy of future investigation.
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PMID:Establishment of donor hematopoiesis after hydroxyurea-induced aplasia following allograft failure in a patient with monosomy 7 variant of childhood chronic myelogenous leukemia. 265 Jul 93


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