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)

We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute non-lymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1,320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (+/- SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74 +/- 9%; acute nonlymphoblastic leukemia = 50 +/- 11%; and chronic myelogenous leukemia = 55 +/- 11%. Actuarial relapse rates for these three diagnoses were 19 +/- 9%, 17 +/- 11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59 +/- 7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.
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PMID:Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission. 329 91

Serum ferritin levels were monitored in nine patients with acute lymphoblastic leukemia (ALL), nine patients with acute nonlymphoblastic leukemia (ANLL), four patients with chronic myelogenous leukemia (CML), three patients with non-Hodgkin's lymphoma (NHL), and three patients with severe aplastic anemia (SAA) undergoing bone marrow transplantation (BMT) for hematologic malignancies or aplastic anemia. Serum ferritin analysis was performed before and after BMT at monthly intervals and/or according to the clinical condition of the patient. Serum ferritin increased considerably during the first 3 months following BMT and then decreased in patients with an uncomplicated course. Ferritin levels in the serum of patients who had undergone BMT decreased gradually when complete remission was achieved, but increased with any clinical complication. Thus, elevation of serum ferritin concentration was predictable for clinical complications and for relapse. Patients with acute leukemia with serum ferritin levels above 400 micrograms/l at time of BMT had a risk of relapse within 1 year, triple that patients with lower ferritin levels. All patients who underwent BMT to treat severe aplastic anemia have completely recovered. Accordingly, following an initial increase after BMT, serum ferritin levels returned to normal and remained so in line with the patients' good clinical condition. The findings indicate that serum ferritin yields useful information in the clinical evaluation of patients undergoing BMT.
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PMID:Serum ferritin in patients undergoing bone marrow transplantation. 330 Sep 50

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.
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PMID:Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies. 331 Dec 1

One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.
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PMID:Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. 333 86

Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.
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PMID:Immunoglobulin allotypes Gm and Km in hematologic malignancies. 334 38

Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c-sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in
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PMID:C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies. 345 50

The Seattle Marrow Transplant Team treated about 130 patients (age 4-68 yr) for hematologic cancer with supralethal chemoradiotherapy and bone marrow transplantation (BMT) from the normal genetically identical twin. The procedure was well tolerated. The principal problem was tumor resistance. Nevertheless, BMT for acute leukemia in relapse still cured about 20% of the patients. Moreover, BMT performed while in complete remission cured about 50% of patients with acute lymphocytic leukemia or acute nonlymphocytic leukemia. Sixteen patients received transplantation in the chronic phase of Ph1+ chronic granulocytic leukemia (CGL). All showed disappearance of all Ph1+ cells. Two died of pneumonitis. Of the 14 who are alive, 3 continue to have CGL 37-76 months after BMT and 11 remain in complete hematologic and cytogenetic remission without any Ph1+ metaphases at 31-108 months (median = 68) after BMT. Thus the Ph1-positive clone can be ablated and blast crisis prevented. BMT in the accelerated or blastic phase was far less effective. Syngeneic BMT also benefited or cured patients with lymphoma, hairy-cell leukemia, and multiple myeloma. Therefore, BMT should be considered for every patient who has a hematologic cancer and an identical twin.
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PMID:Identical-twin (syngeneic) marrow transplantation for hematologic cancers. 352 68

During the past 10 years, 86 patients 30 to 54 years of age with hematologic malignancies were prepared with high-dose radiochemotherapy and received histocompatible bone marrow grafts. Thirty-four of these patients are surviving for 4 months to 9 years (median, 26 months) following marrow transplantation and 32 of them are in continuing complete remission (CR). Disease-free survival is 44% for 37 patients who were in first remission of acute leukemia or in the chronic phase of chronic granulocytic leukemia (CGL), 23% for 39 patients whose leukemia had relapsed at least once before transplantation or who had advanced stages of CGL, and 60% for ten patients who had hematologic malignancies other than leukemia. The median age of the surviving 34 patients is 36 years (range, 30 to 43 years). The incidence of moderate to severe acute graft-v-host disease (GVHD) was 48% and of chronic GVHD, 26%. The major causes of failure were interstitial pneumonia in 31 patients (24 of whom had antecedent acute GVHD) and recurrent leukemia in 12 patients (11 of whom had either never entered a CR or had relapsed at least once with acute leukemia or had progressive CGL before transplantation). Our data warrant further prospective studies in patients with hematologic malignancies who are older than 30 years.
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PMID:Bone marrow transplantation for hematologic malignancies in patients aged 30 years or older. 353 23

The interferons are an important first member of a family of biologic response-modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Alpha interferon is the most extensively studied interferon species. Although antitumor activity has been seen both in vitro and in vivo in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. More than 90 percent of patients with hairy cell leukemia have a sustained recovery of their peripheral blood cell counts with alpha interferon therapy. Approximately 50 percent of patients with low-grade non-Hodgkin's lymphoma and cutaneous T cell lymphoma demonstrate a response to alpha interferon. More than 80 percent of patients with chronic myelogenous leukemia have a response to alpha interferon, and in one study, nearly half of the patients with response had complete suppression of the Philadelphia chromosome clone on at least one examination. Ongoing clinical trials are addressing such issues as optimal dosage, duration of alpha interferon therapy, and combinations of alpha interferon with other biologic agents, chemotherapy drugs, and radiation.
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PMID:Alpha interferon in the treatment of hematologic malignancies. 353 96

The clinical development of the alpha interferons has now progressed through initial Phase I and II trials into extensive controlled clinical trial designs. Alpha interferon has been a prototype of other biological agents that are now in clinical development. These agents operate through fundamentally different mechanisms of action than conventional chemotherapy and have produced a unique profile of side effects as well as response patterns. Time to response is generally longer than with chemotherapy, and dose-response and schedule-dependency questions continue to be explored for most tumor types. Although response rates have been low against most solid tumors when alpha interferon is used as a single agent, it has demonstrated a surprisingly wide range of efficacy in hematologic malignancies. These include tumors of presumed B-cell, T-cell, and myeloid lineages. In some diseases, e.g., hairy cell leukemia and chronic myelogenous leukemia, alpha interferon is broadly effective; it appears to considerably reduce or occasionally eliminate the malignant clone while normalizing the peripheral blood counts in most patients. In other diseases, alpha interferon appears destined to play a major role as part of combination therapy or in maintenance or consolidation therapy. In other disease settings, alpha interferon's role continues to be explored as part of combination therapy, adjuvant therapy, or as local-regional therapy. The full potential of alpha interferon as an antineoplastic agent will not be determined for many years. In this paper, the results from the first 5 years of widespread clinical testing are reviewed.
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PMID:Clinical overview of alpha interferon. Studies and future directions. 354 85


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