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)

Allogeneic BMT is treatment of choice for acute leukaemias(AL) and chronic granulocytic leukaemia (CGL). In the period form 1989 till 1997 36 allogeneic BMT have been performed for patients with AML, ALL and CGL using HLA matched related donors in University Medical Centre Ljubljana. The procedure was successful in 80% of patients with CGL and in 50% of patients with AL. The most frequent cause of death in CGL patients was CMV pneumonitis, relapse in patients transplanted for ALL, while in patients transplanted for AML beside relapse we observed four deaths due to complications of BMT ( acute GVHD, VOD, thrombotic thrombocytopenic purpura, liver failure due to hepatitis).
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PMID:Allogeneic BMT for acute leukemia and chronic granulocytic leukemia in University Medical Centre Ljubljana-Slovenia. 991 41

Between February 1995 and August 1997, 11 children (eight males, three females) aged 4-16 years (median 7 years) underwent allogeneic PBPC transplantation for treatment of hematological disorders. Seven patients with acute leukemia (n = 5 ALL, n = 1 AML) or lymphoma (n = 1) received primary allogeneic PBPC transplantation, four patients received a second allotransplantation for graft failure (n = 1 AML, n = 1 sickle cell anemia) or disease recurrence (n = 1 ALL, n = 1 MDS). Five donors were HLA-identical siblings, five were 0-1 antigen mismatched family members and one was a matched unrelated donor. Donors received G-CSF 10-12 microg/kg/day for 3-7 days, and underwent one or two leukaphereses. The median cell yield per donor expressed per kg of recipient body weight was as follows: mononucleated cells 10.8 x 10(8)/kg (range 4.7-21.2); CD34+ cells 8.6 x 10(6)/kg (range 3.2-22); CD3+ cells 3.7 x 10(8)/kg (range 2.7-7.5). All patients achieved an ANC >0.5 x 10(9)/l after a median of 12 days (11-18). An unsupported platelet count >50 x 10(9)/l was reached 15 days (13-21) after PBPC transplantation; four patients failed to reach this threshold. Acute GVHD (aGVHD) grades II to IV occurred in eight (73%) patients: seven of them experienced grade III-IV aGVHD. Seven patients evaluable for chronic GVHD (cGVHD) were scored as absent in five, limited in one and extensive in one patient. As of September 1997, six patients (55 %) were alive between 60 and 938 days post-transplant (median follow-up 274 days); four patients with malignancy were alive in CR after primary allotransplantation, two patients were alive after a second PBPC transplant. Five patients have died with the main causes of death being aGVHD (n = 3), ARDS (n = 1), relapse of the underlying disease (n = 1). In conclusion, despite the limited number of patients, these preliminary results indicate that PBPC may be considered as an alternative to bone marrow for allografting also in children.
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PMID:Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers. 998 87

Donor leukocyte infusions (DLI) from the original marrow donor have been shown to induce remission in patients with relapse after BMT. We analyzed factors that were associated with remission. Twenty-six patients with a relapse after T cell depleted BMT received DLI. The following pre-DLI factors were analyzed: sex and age of the patients and donors, GVHD after BMT, indication for DLI, percentage of donor T lymphocytes in the patient at the time of DLI, interval between relapse and DLI, and number of T lymphocytes infused. Remission was achieved in 11 of 15 patients (73%) treated for relapsed CML and in one of 11 patients (9%) treated for relapsed AML, ALL or RAEB-t (P = .002). Two of 13 patients (15%) with < or =40% of T lymphocytes from donor origin attained remission compared with 10 of 13 patients (77%) with >40% (P = .002). Two of 13 patients (15%) with an interval of < or =18 months between BMT and first DLI entered remission compared with 10 of 13 patients (77%) with an interval of >18 months (P = .002). Multivariate analysis demonstrated that indication for DLI (CML versus AML/ALL and RAEB-t) and the percentage T lymphocytes from donor origin (< or =40 versus >40) were significantly correlated with remission (P = .03). The occurrence of GVHD post DLI was highly associated with achievement of remission (P = .0001). DLI res ults in remission in a high percentage of patients with relapsed CML after BMT. The percentage of T lymphocytes from donor origin still present in the patient at the time of DLI is highly correlated with achievement of remission.
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PMID:In relapsed patients after lymphocyte depleted bone marrow transplantation the percentage of donor T lymphocytes correlates well with the outcome of donor leukocyte infusion. 1003 29

Long-term outcome of 23 acute myeloid (AML, n=16) or lymphoblastic (ALL, n=7) leukemia patients who had received immunotherapy for treatment of persistent or recurrent disease 1.5-26 (median 4) months after allogeneic transplantation was studied to determine eventual survival. Immune manipulation comprised donor leukocyte infusion (n=18), interferon-alpha2b and/or interleukin-2 (n=15), and cyclosporine withdrawal (n=11) in various combinations. Graft-versus-host disease (GVHD) developed in 12 patients. Thirteen of 20 evaluable patients responded; 6 relapsing again. Eight patients died of toxicity, and 10 of progressive disease at 3-206 weeks (median 11). Five patients (3 AML, 2 ALL) are alive in remission with GVHD 2-46 months (median 23) after immunotherapy with Karnofsky scores of 70-100% (median 80). The overall survival of the whole group is 1-206 weeks (median 12), with an actuarial survival of 22% at 2 years. The development of GVHD was associated with superior survival in multivariate analysis (P=.007). Seven patients received immunosuppression because of the severity of GVHD (grade III/IV acute or extensive chronic): 3 died of GVHD, 3 improved but relapsed concomitantly, and 1 is alive in remission with extensive chronic GVHD. Four episodes of extramedullary relapse (granulocytic sarcomas) were seen in 3 patients with AML whose marrow remained in remission. We conclude that GVHD appears to be inseparable from graft-versus-leukemia in relapsed acute leukemia patients undergoing immunotherapy with a high proportion of patients dying due to toxicity or progressive disease, and isolated extramedullary relapse seems to be unusually common.
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PMID:Long-term follow-up of relapsed acute leukemia treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus-leukemia, and the problem of extramedullary relapse. 1004 23

From March 1994 to September 1997, 30 patients with hematological malignancies (12 ANLL, 10 CML, four ALL and four multiple myeloma) received HLA-identical allogeneic bone marrow transplants with the marrow graft selectively depleted of CD4+ lymphocytes and the CD8+ cell content adjusted to 1x10(6)/kg. Total depletion of CD4+ and partial depletion of CD8+ lymphocytes was carried out by an immunomagnetical method. All patients were considered as having high risk for developing GVHD by at least one of the following criteria: patient age >35 years; donor age >35 years; donor multiparity or marrow from an unrelated donor. Twenty-four cases received marrow from an identical sibling and six from an unrelated donor. In order to assess the role of methotrexate (MTX) in addition to cyclosporin A (CsA) after transplant, patients were randomly assigned to received either CsA alone (n = 15) or CsA plus a short course of MTX (n = 15). No case of primary graft failure was observed, but two patients developed late graft failure. Six patients presented grade II acute GVHD and no case of severe III-IV GVHD was seen. The actuarial probability of developing grade II-IV acute GVHD was 25.9+/-9.6% for the entire population. Patients receiving post-transplant CsA + MTX had significantly less probability of acute GVHD than those receiving CsA exclusively (6.7+/-6.4% vs. 50.5+/-17.8%, P = 0.03) and the schedule of post-transplant immunosuppression was the only factor associated with the incidence of acute GVHD in a multivariate analysis. The actuarial incidence of chronic GVHD for the entire population was 31.8+/-12.5, and there was no significant difference between both groups with additional prophylaxis. Four patients with CML and three with ANLL relapsed: the actuarial probability of remaining in complete remission for all patients was 53.6+/-17.3%. For patients with acute leukemia, the probability of remaining in complete remission did not differ significantly between those transplanted in first complete remission and those receiving a transplant in more advanced phases of the disease (87.5+/-11.6% vs. 72.9+/-16.5%; P = 0.44). The incidence of mixed chimerism assessed by PCR was 34%. Nineteen patients are alive between 2 and 43 months post-transplant, the probability of overall survival being 57.8+/-10.4%. Our data indicate that this method of selective T cell depletion is very effective in preventing acute GVHD in high risk patients, particularly when used in combination with post-transplant CsA + MTX.
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PMID:Prevention of graft-versus-host disease in high risk patients by depletion of CD4+ and reduction of CD8+ lymphocytes in the marrow graft. 1010 May 57

In the last 3 years, 14 children with high-risk leukemia (11 ALL, 2 AML and 1 CML) underwent cord blood transplantation from unrelated HLA-mismatched donors at a median of 99 days from the start of search. Eight patients were transplanted in second CR, one in accelerated phase, three at relapse and two patients in first CR. Conditioning regimen (fractionated TBI, etoposide, CY and anti-lymphocyte serum) and prophylaxis of GVHD (CsA and 6-methylprednisolone) were identical for all patients. Neutrophils >0.5x10(9)/l were reached at a median of 33 days from transplant, but in four cases we observed an autologous hematopoietic reconstitution (three spontaneous, one after autologous BM rescue). Acute and chronic GVHD were observed in 10/14 and 3/8 evaluable cases, respectively. Three patients died of transplant-related toxicity and three patients relapsed. The probabilities of event-free, disease-free and overall survival were 50, 53 and 64%, respectively. Cord blood transplant from HLA-mismatched unrelated donor is a valid option for the treatment of children with high-risk leukemia. With our eligibility criteria, conditioning regimen and prophylaxis of graft-versus-host disease, the main obstacles to successful transplant were represented by graft failure and fatal acute GVHD.
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PMID:Umbilical cord blood transplant from unrelated HLA-mismatched donors in children with high risk leukemia. 1021 84

Ten patients with acute leukemia (AL) in early relapse after allo-BMT were treated with a modified MEC (mitoxantrone, etoposide and Ara-C) regimen followed by donor PBPC collected after mobilization with G-CSF. Seven patients achieved CR or had normal hemopoietic reconstitution: two had an early relapse at days +53 and +48, two patients died from acute GVHD at days +31 and +96, one died of interstitial pneumonia at day +55, and two patients experienced long-term survival. One patient with refractory disease and nodal involvement who did not respond to the first BMT had overt expansion of the leukemia at day +36; one patient with Ph+ ALL and one with ANLL evolving from MDS, both with skin involvement, had blast cells in peripheral blood at day +27 and +26, respectively. Transient cytopenia occurred in all patients; a normal granulocyte and platelet count was achieved within 3 weeks in all patients but one; acute GVHD occurred in six patients, and four had chronic GVHD. This approach is feasible in patients in early relapse after allo-BMT. It assists prompt re-establishment of normal donor hematopoiesis avoiding the prolonged cytopenia observed after donor lymphocyte infusion in AL patients relapsed after allo-BMT.
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PMID:Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. 1021 92

The success of allogeneic stem cell transplantation (allo-SCT) in children is mainly affected by relapse or graft rejection. We have recently shown in a study of 55 patients with acute leukemias (ALL 21, AML 20 and MDS 14), that patients who demonstrate increase amounts of autologous marrow repopulation (increasing mixed chimerism) have a significantly enhanced risk of relapse (P < 0. 0001). Based on these findings, we asked whether post-transplant relapse can be prevented by withdrawal of immunosuppression and/or by donor lymphocyte infusion (DLI). We describe the results of a pilot study where adoptive immunotherapy was used to treat 12 patients (five ALL, three AML, four MDS) who showed increasing mixed chimerism (MC) post-transplant. A response to immunotherapy, defined as the re-establishment of complete chimerism (CC) and continuous complete remission (CCR), was achieved in four patients (two ALL, two AML) following withdrawal of CsA and in a further six patients (three ALL, three MDS) after additional DLI. One ALL patient, who initially responded to DLI, developed severe GVHD that required further immunosuppression. GVHD was controlled but this patient subsequently relapsed. Another patient with ALL became a CC but developed an isolated relapse in the bone marrow 260 days later. One patient with MDS developed severe GVHD after DLI and died. Two children (one AML and one MDS) did not show any response to interventional treatment and died due to relapse. Of the 12 patients treated, seven remain in CCR at a median follow-up of 747 days (range 351-1109 days). In summary, these results provide evidence that increasing MC can be used to guide adoptive immunotherapy strategies and that these treatment modalities can be used to prevent relapse in children with acute leukemias or MDS after allo-SCT.
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PMID:Prevention of relapse in pediatric patients with acute leukemias and MDS after allogeneic SCT by early immunotherapy initiated on the basis of increasing mixed chimerism: a single center experience of 12 children. 1060 32

Between October 1995 and October 1998, 24 children aged 9 months to 17 years (median 11 years) underwent cytokine-mobilized allogeneic peripheral blood stem cell (PBSC) transplantation for treatment of hematological disorders. All of the transplants were the first allogeneic transplant for the recipient. Twenty patients were transplanted for hematological malignancies (ALL = 8, AML = 6, CML = 4, MDS = 2) and four patients were transplanted for non-malignant disease (thalassemia major = 2, Wiskott-Aldrich syndrome = 1, Kostmann's syndrome = 1). Nineteen donors were HLA-identical siblings, four were HLA-matched or single antigen mismatched parents, and one was a syngeneic transplant. Donors aged 8 to 38 years (median 15 years, 14 donors <18 years) received G-CSF 10 microg/kg/day subcutaneously beginning 4 days before PBSC collection and were submitted to one to three leukapheresis collections. The median CD34+ cell yield was 7.8 x 106 cells/kg recipient body weight. All patients achieved an ANC >0.5 x 109/l after a median of 13 days (range 10-21). Twenty-three patients eventually achieved platelet transfusion independence. One patient died on day 63 without ever achieving platelet transfusion independence. Four patients received platelet transfusions to maintain a platelet count well above 20 x 109/l due to bleeding complications. Of the 19 evaluable patients, the median time to a non-transfused platelet count of 20 x 109/l was 12 days (range 0-44). Ten of 23 at-risk patients developed acute GVHD grades II to IV, with grades III to IV in four patients. Twelve of 19 patients followed for at least 100 days have developed chronic GVHD (extensive = 2, limited = 10) with an actuarial risk of chronic GVHD of 75% at 1 year. The Kaplan-Meier estimate of event-free survival is 65% at 2 years. Four patients died (GVHD = 3, VOD = 1), three patients relapsed, and one patient with thalassemia major had a late graft failure with autologous recovery. Based upon our experience, allogeneic PBSCT is safe for both pediatric donors and recipients and engraftment of neutrophils and platelets is rapid. Bone Marrow Transplantation (2000) 25, 13-18.
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PMID:Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD. 1065 8

We describe a 5-year-old girl with Ph(+) CML who received a cord blood transplant in a second accelerated phase after a very early lymphoid blast crisis. She was induced into CR by ALL-directed chemotherapy and then maintained with IFN-alpha2b together with weekly rotational chemotherapy. Nineteen months after diagnosis, her mother gave birth to an HLA-compatible sibling, whose cord blood was cryopreserved. The patient's second acceleration occurred 22 months after the CML diagnosis. The subsequent conditioning regimen included busulfan 16 mg/kg, Ara-C 12 g/m2 and melphalan 140 mg/m2. In order to prevent GVHD, CsA alone was administered, 3 mg/kg i.v. per day for a total of 40 days. The total number of nucleated cells infused was 0.8 x 108/kg, with CD34+ cells 1.8 x 106/kg and CFU-GM 1 x 104/kg. Engraftment occurred on day +35. Respiratory distress, severe VOD and grade II acute gastrointestinal GVHD complicated the post-transplant period. No chronic GVHD occurred. The girl is alive 23 months after transplantation with complete donor chimerism; both Ph chromosome and bcr/abl RNA are negative. Bone Marrow Transplantation (2000) 25, 213-215.
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PMID:A successful cord blood transplant in a child with second accelerated phase chronic myeloid leukemia following lymphoid blast crisis. 1067 84


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