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)

The in vitro sensitivity of human chronic myeloid leukemia-blast crisis and chronic phase (CML-BC and CML-CP, respectively) cells as well as adherent cell-depleted, T lymphocyte-depleted normal bone marrow cells (A-T-NBMC) to various concentrations of mafosfamide (ASTA Z7654), was examined by colony formation assay in the presence of IL-3 and GM-CSF, to test the possibility of purging of BMC from CML cells. Colony formation by CML cells was inhibited more efficiently than by NBMC. After the incubation with 50 micrograms/ml or 100 micrograms/ml of mafosfamide, the growth of leukemic CFU-GM was totally abrogated in 2/11 or 9/11 cases of CML-BC and in 1/7 or 6/7 cases of CML-CP, respectively. At the same time the CFU-GM arising from normal BMC were not inhibited totally with 50 or 100 micrograms/ml of the drug in any of five experiments. CML cells were still unable to form secondary colonies, while normal BMC were capable of regrowth. The CD34+ cells isolated form CML-BC and CML-CP patients were also more susceptible to mafosfamide cytotoxicity in comparison to CD34+ cells derived from NBMC. To confirm the possibility of purging, CML-BC cells were mixed with NBMC (1:1) and incubated with mafosfamide. Finally, the growing colonies were examined for the presence of bcr/abl hybrid gene by reverse transcriptase-Taq polymerase chain reaction (RT-PCR) and specific hybridization. The bcr/abl gene was not detected in the colonies growing after 100 micrograms/ml, and the signal was diminished after incubation with 50 micrograms/ml of mafosfamide, as compared to control. These results strongly suggest that high concentrations of mafosfamide may be useful for the purging of autologous BMC from CML cells.
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PMID:Successful mafosfamide purging of bone marrow from chronic myelogenous leukemia (CML) cells. 813 96

Allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) offers the only significant chance of cure for this disease. About 50% of patients transplanted in the 1980s appear to be cured and with subsequent advances, it is suggested that more patients transplanted in the 1990s will be cured. Cyclophosphamide (Cy) (120 mg/kg) followed by fractionated total body irradiation (TBI) (Cy2/TBI) has been usually employed in preparation for BMT. Alternative regimens of Busulfan (Bu) (16 mg/kg) and Cy (120 mg/kg) (Bu/Cy2) or Bu (16 mg/kg) and Cy (200 mg/kg) (Bu/Cy4) have more recently been employed. At least three studies of Bu/Cy2 or Bu/Cy4 have given encouraging results. Two ongoing randomized studies of Bu/Cy2 versus Cy2/TBI have shown no difference in the event free survival (EFS). In addition, two ongoing randomized studies of Bu/Cy4 versus Cy (200 mg/kg) plus TBI (Cy4/TBI) show no significant differences in EFS. It appears that Bu/Cy regimens are as effective as Cy/TBI regimens. The choice of one regimen over the other depends on matters other than therapeutic efficacy.
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PMID:Busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation for marrow transplantation in chronic myelogenous leukemia--a review. 825 96

Synthetic oligodeoxynucleotides complementary to the break-point junction of bcr-abl transcripts selectively inhibit the proliferation of Philadelphia-positive leukemic cells, but residual leukemic cells persist in antisense oligodeoxynucleotides-treated cultures. Cyclophosphamide derivatives such as mafosfamide and 4-hydroperoxycyclophosphamide are used at high doses for purging of Philadelphia leukemic cells from marrows but such treatment can be associated with delayed engraftment and prolonged cytopenias. To develop a more effective procedure that might optimize the killing of leukemia cells and the sparing of normal hematopoietic progenitor cells, a 1:1 mixture of Philadelphia leukemic cells and normal bone marrow cells was exposed to a combination of a low dose of mafosfamide and bcr-abl antisense oligodeoxynucleotides and assayed for growth ability in clonogenic assays and in immunodeficient mice. Bcr-abl transcripts were not detected in residual colonies, and cytogenetic analysis of individual colonies revealed a normal karyotype. Normal but not leukemic hematopoietic colonies of human origin were also detected in marrows of immunodeficient mice 1 mo after injection of the treated cells. Our results indicate that a combination of a conventional chemotherapeutic agent and a tumor-specific antisense oligodeoxynucleotide is highly effective in killing leukemic cells and in sparing a much higher number of normal progenitor cells as compared with high-dose mafosfamide treatment. This offers the prospect of a novel and more selective ex vivo treatment of chronic myelogenous leukemia.
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PMID:Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr/abl antisense oligodeoxynucleotides combined with mafosfamide. 832 84

The outcomes of bone marrow transplantation (BMT) performed at the Institute of Haematology and Blood Transfusion from April 1988 to December 1994 in 31 patients with chronic myelogenous leukemia are presented. Age of the patients range from 18 to 49 years, median 34 years. Male:female ratio was 1.58:1. The conditioning regimen consisted of Cyclophosphamide and total body irradiation (TBI) or Busulfan and Cyclophosphamide. The results are evaluated as of January 1, 1995. Nineteen patients (61.3%) are alive, 12 patients (38.7%) died. The causes of death are discussed. The median time of follow up all patients is 10.4 months, range 0.3-81.5. The median time of follow up of surviving patients is 21.8 months, range 2.5-81.5. Probability of 2 years survival by Kaplan-Meier analysis is 58 +/- 10%. Of the 24 transplanted in the first chronic phase, 18 patients are alive. Of the 7 transplanted in advanced phase of the disease, 1 patient is alive. Of the 27 patients, who received bone marrow from an HLA identical sibling, 19 are alive. Of the 4 patients who received bone marrow from other donor than an HLA identical sibling, none is alive. Acute GvHD III.-IV. grade developed in 5 patients (16.1%), moderate and severe chronic GvHD developed in 11 patients (31.5%). Cytogenetic relapse was diagnosed in 1 patient, hematological relapse in 2 patients. Karnofsky scores of patients surviving after BMT range from 30% to 100%, median 90%.
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PMID:[Treatment of chronic myeloid leukemia with bone marrow transplantation at the Institute of Hematology and Blood Transfusion in Prague]. 857 99

A 9-year-old with chronic myelogenous leukemia (CML) who received bone marrow transplantation from an unrelated donor (UBMT), is reported. He also suffered from congenital heart disease (CHD) consisting of corrected transposition of the great arteries and dextrocardia. The cardiac output was within normal limits. The conditioning regimen included busulfan, melphalan, ALG and TLI. Cyclophosphamide was not used because of it cardiotoxicity. The HLA-phenotype of the donor was identical with that of the patient. DNA typing showed was haplodentical DRB1. The patient is alive 18 months after the UBMT. This case showed that UBMT was possible in a CML patient with CHD, without congestive heart failure.
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PMID:[Bone marrow transplantation from an unrelated donor in patient with congenital heart diseases]. 882 86

The Bone Marrow Transplantation Program in Belarus was founded in 1992, and in 1993, a Bone Marrow Transplantation Centre was created in Minsk. From February 1994 to April 1996, 19 allogeneic bone marrow, 16 autologous bone marrow and 10 autologous peripheral blood stem cell transplantations were performed. Reasons for transplantation included chronic myeloid leukemia, multiple myeloma, severe aplastic anemia, acute myeloid leukemia, acute lymphoblastic leukemia, progressive myelofibrosis, Hodgkin's disease, non-Hodgkin's lymphoma, and neuroblastoma. Among the patients were two liquidators involved in the Chernobyl cleanup activity, both of whom underwent allogeneic bone marrow transplantation. A variety of ablative preparative regimens were used, and blood progenitor cells were mobilized by treatment with Cytoxan and granulocyte colony-stimulating factor. Therapy-related deaths resulted from graft-versus-host disease, septic shock, veno-occlusive disease bleeding and intestinal pulmonary fibrosis. Because the transplantation procedures were carried out on people who continued to be exposed to low-level irradiation, the post-transplantation period included a conservative strategy for prevention of graft-versus-host disease. There was nothing unusual about the post-transplantation period, although uncertainty about the continuing radiation dose should be taken into account when interpreting these data.
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PMID:The Chernobyl governmental program: two years of experience at the Belarusian Bone Marrow Transplant Centre. 936 16

In a retrospective single centre study we examined the outcome of five different therapy approaches in 48 patients in whom a relapse of CML (13 cytogenetic relapses, 35 hematological relapses: 10 chronic phase (CP), nine accelerated phase, 16 blast crisis) occurred after allogeneic BMT. Cyclosporin A (CsA) withdrawal, interferon alpha-2b (IFN-alpha) therapy, donor leukocyte transfusions (DLT), second transplantation (2nd BMT), and chemotherapy (CTX) alone were used and studied for their response rates. Patients who achieved a complete hematologic and cytogenetic remission (CR) were studied for BCR-ABL transcripts and for their chimerism status by PCR. A strong antileukemic effect was observed after abrupt CsA withdrawal, with 10 of 20 patients achieving a CR (50%). All 10 patients with early stage (nine cytogenetic and one CP), but none of the patients with advanced disease recurrence, responded to CsA withdrawal. IFN-alpha induced in five of 11 patients (45%) a stable cytogenetic remission, whereas treatment with DLT induced a CR in only two of 14 patients (14%). A second transplant was performed in six patients. Three of six patients (50%) survive disease-free at a median of 19 months after the 2nd BMT (range 10-25). The use of CTX alone did not induce a remission.
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PMID:A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. 946 77

Graft versus host disease (GVHD) and recurrence of basic disease are major obstacles to a successful allogeneic bone marrow transplantation (BMT) outcome. One of the possibilities of maintaining the therapeutic potential of marrow allografting in the absence of GVHD is to intensify the conditioning regimen administered pre-T-cell depleted BMT in order to compensate for the loss of GVH related graft versus leukemia (GVL) effect. In order to do so we used a preparative regimen consisting of three alkylating agents-Busulfan (BU), Thiotepa (TTP) and Cyclophosphamide (CY)-for T-cell depleted allogeneic stem cell transplantation (SCT) instead of the standard BU-CY protocol. The effect of this intensified regimen was investigated in 30 consecutive leukemia patients who underwent T-cell depleted SCT from HLA identical siblings. Sixteen of the patients were males and 14 females, of median age 24 (5-43) years. Fourteen patients had acute myelogenous leukemia (AML), ten acute lymphoblastic leukemia (ALL), four chronic myelogenous leukemia (CML) and two myelodysplastic syndrome. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was normal, with WBC >1.0x10(9)/l at day +18 (10-32), ANC >0.5x10(9)/l at day +21 (9-33) and platelets >25x10(9)/l at day +30 (14-69). Regimen related toxicity (RRT) was moderate and transplant related complications comparable to other conventional conditioning protocols. Overall survival and disease free survival (DFS) at 60 months follow up was 50%. Only three patients (10%), with ALL, relapsed and subsequently died. From the current data it would appear that TTP does not significantly improve BMT outcome in patients with leukemia, when compared to the standard BU-CY conditioning. However, our results with the BU-TTP-CY combination followed by T-cell depleted allogeneic SCT could provide the basis for a prospective randomized study comparing this protocol with the standard BU-CY regimen.
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PMID:The role of thiotepa in allogeneic stem cell transplantation in patients with leukemia. 1057 41

Seventeen patients and their family donors HLA 2 - 3 antigen mismatched of 2 - 3 loci were enrolled in the study of haploidentical transplants from February 1999 to March 2001. Among patients with leukemia, most patients were classified as high risk. Eleven patients with ALL were all in more than second remission but one was in relapse. Patients with AML were one in CR1, one in CR2 while 4 patients with CML were two in CP and two in AP. The male-to-female ratio was 14:3 and the median age was 15 (range from 8 to 35). Conditioning regimens included Ara-C 3.0 g/m(2), 2 times per day x 3 d, on day 7, 6 and 5 pre-transplantation, CTX 45 mg/(kg per d) x 2 d on day 5 and 4 pretransplantation. TBI with 1000 cGy by 2 fractions on day 2 and 1 pretransplantation. The fresh and unmanipulated marrow was infused on day 0. Donors were received G-CSF (Lenograstim) at 3 - 4 microg/(kg per d) x 7 d. The BM cells were collected on eighth day. In GVHD prophylaxis, CSA, MTX, ATG (Antithymocyte globulin, Rabbit Fresenius S) and MMF (mycophenolate mofetic) were used in different periods. The dose of CSA was 1.5 mg/(kg per d) on day 7 to 1 pretransplantation, then 3 mg/(kg per d) from day 1 pretransplantation. MTX was 15 mg/m(2) on day 1 and 10 mg/m(2) on day 3, 6 and 11 posttransplantation. ATG was administered day 4 to 1 pretransplantation at 5 mg/(kg per d) and MMF dose was 1.0 g/d from day 7 posttransplantation. All patients established successful engraftment after initial transplantation. The median days of neutrophil exceeding 0.5 x 10(9)/L and platelet exceeding 20 x 10(9)/L were 18 (range 13 - 23) and 20 (range 16 - 32) days, respectively. Patients were monitored up to day 100 for the sign of aGVHD. The established grades II to IV aGVHD occurred in 5 out of 17 patients (29.4%). Eleven patients were surviving at a median follow-up of 13 months (range 3 - 27 months). Six out of the 17 patients died those 3 of them died of severe aGVHD, 2 of infection and 1 of leukemia relapse. Severe regimen-related toxicities were not experienced in all patients. The median follow-up period was 13 (range 3 - 27) months. Eleven patients were alive in disease-free situation with a Karnofsky performance status of 100%. This could be caused by the low overall incidence of aGVHD as a result of BM primed with G-CSF. The four-agent of immunosuppressive combined prophylaxis against GVHD in different periods may be highly effective.
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PMID:[Successful engraftment of T-cell undepleted haploidentical transplants by donor primed with G-CSF and additional use of ATG and MMF for recipients]. 1251 19

Allogeneic haemopoietic stem cell transplantation was initially considered as a means of delivering supralethal doses of chemotherapy with or without total body irradiation for the treatment of malignancy. However, it has become clear that this mode of therapy does not eradicate the malignancy in many patients and its benefit is largely due to the immune mediated graft versus malignancy effect. This has led to development of alternative strategy to utilize a less intensive preparative regimen pre-transplantation that provides sufficient immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus allowing the evolution of a graft versus malignancy effect post-transplantation. Since September 1999, we had carried out 10 cases of allogeneic peripheral blood stem cell transplantation: one case of aplastic anaemia, four cases of acute myeloid leukemia (AML) in first remission, and five cases of chronic myeloid leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from transplantation was rapid with no or brief period of neutropenia or thrombocytopenia. Engraftment was established by determining donor's short tandem repeats in the recipient's bone marrow at day 30, 60 and 100 post-transplantation. Seven cases (70%) show partial or complete donor's chimerism by day 30 indicating successful engraftment. No treatment mortality was noted at day 100. Graft versus host disease was generally limited. Up to the date of reporting, two patients with CML had graft failure, one was successfully re-transplanted later. Two patients with AML had since relapsed and passed away. The others remain alive and well. The cost of transplantation on average was estimated to be about a quarter of that using a myeloablative regimen. It appears that this treatment strategy is a promising approach for the management of blood disorders.
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PMID:Allogeneic haemopoietic stem cell transplantation using non-myeloablative conditioning--a local experience. 1456 43


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