Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients received a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with successful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.
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PMID:Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation. 36 30

A 47-year-old patient was treated with allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia in blast crisis. Three months after the procedure he developed bullous pemphigoid (BP) and symptoms suggestive of BP oesophageal involvement, associated with skin and liver acute graft-versus-host disease. The occurrence of BP is exceptional after BMT.
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PMID:Bullous pemphigoid associated with acute graft-versus-host disease after allogeneic bone marrow transplantation. 142 95

A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA-DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB). 149 15

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
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PMID:Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. 155 89

The success of bone marrow transplantation in chronic myelogenous leukemia (CML) is strongly associated with the phase of the disease at the time of transplantation. For allogeneic transplants from siblings with identical human leukocyte antigens, the 3-year survival rate for recipients in chronic phase ranges from 55% to 70%, whereas survival falls to approximately 30% for recipients in accelerated phase and to 0% to 20% for patients receiving transplants during blast crisis. Detailed analysis of data pooled from 405 patients demonstrated that the 3-year probability of relapse was 48% for recipients of T-cell-depleted bone marrow, but only 9% for recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than .0001). Regardless of transplant T-cell status, however, patients who developed chronic graft-versus-host disease (GVHD) were less likely to relapse at 4 years when compared with recipients without chronic GVHD (6% v 24%; relative risk, 3.1; P less than .01). Survival was correlated with severity of acute GVHD and age. Allogeneic bone marrow transplantation from unrelated donors can be useful in expanding the patient population eligible for transplantation. A study of recipients of transplants from unrelated donors showed a 3-year projected survival of 55% for chronic phase patients, and 22% for patients with advanced disease. However, a high rate of graft failure (10%) and grade II to IV acute GVHD can be expected. Preliminary data suggest that ex vivo treatment of autologous bone marrow with interferon can effect complete or partial Philadelphia (Ph) chromosome negative bone marrow mosaicism, although appearance of Ph chromosome negative metaphases may not be persistent. Thus, interferon treatment of autologous bone marrow may play a more significant role in the treatment of CML.
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PMID:Bone marrow transplants in chronic myelogenous leukemia: an overview of determinants of survival. 169 63

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Ninety second bone marrow transplants (BMT) for relapsed leukaemia were carried out in 30 European BMT centres. At second BMT, after further treatment in 64 cases, 43 patients were in complete remission or in chronic phase of CML, and 47 were in continuing relapse, accelerated phase or blast crisis of CML. Seventy patients died, 37 from early transplant-related toxicity and relapse or failure to eradicate leukaemia which occurred in 23. There were 20 survivors. The actuarial disease-free survival was 11% with a relapse probability of 69% at 3 years. Associated with reduced graft-versus-host disease (GVHD) prophylaxis during second BMT, the incidence and severity of acute and chronic GVHD, was increased when compared with the first BMT (P = 0.02, and 0.002 respectively for acute and chronic GVHD). In multivariate analysis survival was shown to be favoured by a prolonged interval between first and second BMT (relative risk 1.3/year, P = 0.02), and no or mild chronic GVHD following first BMT (relative risk 2.3, P = 0.02). Continuing remission was favoured by chronic GVHD occurring after second BMT (relative risk 8.1, P = 0.004). These results confirm the high treatment-related mortality following second BMT, but identify superior survival in selected patients. Improved results might be achieved by further reduction in preparative regimen intensity, and increasing graft-versus-leukaemia reactivity.
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PMID:Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GVHD on continued remission. A report by the EBMT Leukaemia Working Party. 177 78

A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 10(4-5) to one cell in 10(5-6). Eight of 16 patients were negative by two-step PCR 1-39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.
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PMID:Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation. 193 96

Twenty-eight patients aged 16-50 years with chronic myeloid leukaemia (CML) underwent allogeneic bone marrow transplantation (BMT) using human leukocyte antigen (HLA)-identical sibling donors. Of the 28 patients, 21 were in chronic phase, five were in accelerated phase and two were in blast phase at the time of BMT. Twenty-three of the patients survived more than 63-2187 days after BMT, 21 in continuous complete remission and two with haematologic relapse of CML. Two patients died of interstitial pneumonitis and one died of relapsed CML, cerebral aspergillosis and cytomegalovirus enterocolitis. The overall probability of survival at six years was 78% +/- 9% (mean +/- standard error) and of disease free survival 66 +/- 11%. For patients transplanted in chronic phase, the survival probability was 90 +/- 6%, while all of the patients undergoing BMT in chronic phase within the first year after diagnosis were alive with a relapse-free survival of 88 +/- 12%. The actuarial probability of occurrence of acute graft-versus-host disease (GVHD) was 57 +/- 9%, while for Grades II and III GVHD it was 28 +/- 9%. Chronic GVHD occurred in 18 of 25 patients at risk. The majority of patients had a Karnofsky performance score at latest follow-up of at least 90% (range 50-100). We conclude that allogeneic BMT is effective, curative therapy for CML and that BMT performed earlier in the natural history of the disease is associated with the best outcome.
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PMID:Chronic myeloid leukaemia treated by allogeneic bone marrow transplantation from histocompatible sibling donors--an invariably fatal malignancy rendered highly curable. 195 29

We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, -B, and -D antigens of the haplotype not shared; 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurrence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus" (A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of "one-locus"-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients.
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PMID:Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. 224 52


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