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)

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.
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PMID:G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. 1247 77

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

To explore the feasibility of using CD25 monoclonal antibody (Basiliximab) in T-cell undepleted allo-BMT with graft from haplotype-matched related donor for acute GVHD prophylaxis. Twenty-eight patients with leukemia received allo-BMT from HLA two or three loci mismatched related donors. The donors were given G-CSF (Lenograstim) 250 micro g/d for 7 doses prior to marrow harvest. CSA, MTX, ATG and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. ATG 5 mg/(kg.d) was infused from day 4 to day 1 before transplantation and MMF was administered from day 7. In the study group, the patients received additional CD25 monoclonal antibody for aGVHD prophylaxis. CD25 20 mg each by 30 min intravenous infusion on 2 hours before transplantation and day 4 after transplantation was administered while no application of CD25 in the controls. The outcomes of transplantation were compared between the stud y and control groups. The results showed that the median number of CD34(+) cell in graft was 5.9 x 10(6)/kg in the control group and 7.9 x 10(6)/kg in the study group. The median number of CD3(+) cell was 48 x 10(6)/kg and 52 x 10(6)/kg respectively (P > 0.05). All patients showed 100% donor-typed hematopoietic cells after transplantation by cytogenetic evidence. Five out of fifteen patients in the control group experienced II - IV acute GVHD. While none of thirteen in the study group developed the II - IV acute GVHD. However, none in both groups developed extensive cGVHD. The median follow-up duration was 8 (3-15) months in the study group and 26 (15-36) months in control. In the study group, one patient died from transplant related mortality (CMV infection); no one relapsed; and 12/13 patients survived in disease-free situation within the period of follow-up. In the control group, six patients died from transplant related mortality (3 GVHD, 2 infection and 1 relapsed) and 9/15 patients survived in disease-free situation. The one-year probabilities of disease-free survival (DFS) in two groups were significantly different (P < 0.05). It is concluded that the transplant from haploidentical donors used CD25 antibody is effective and feasible in preventing acute severe GVHD and improving DFS. The major histocompatibility barrier in the haploidentical related allo-BMT could be crossed by donors primed with G-CSF and GVHD prophylaxis with CD25 antibody in the hosts.
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PMID:[A clinical study of haploidentical and G-CSF primed bone marrow transplantation by using CD25 for aGVHD prophylaxis]. 1251 46