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)

We present the results of a prospective, randomised study comparing PBPC and BM focusing on engraftment, acute and chronic GVHD and survival. Forty patients with haematological malignancies received HLA-identical sibling BM (group A) or PBPC (group B). Evaluable patients were 19 (A) and 18 (B). Median age was 35 (17-56) in A and 29.5 (9-51) in B. Conditioning was mainly Bu-Cy2; GVHD prophylaxis was CSA-MTX. PBPC were harvested after 5 days of G-CSF 10 microg/kg/day. Median days for an ANC >0.5 x 10(9)/l was 18 (13-30) in A and 16 (11-25) in B (P = 0.10). Platelets >20 x 10(9)/l occurred at +17 (10-40) in A and +12 (9-36) in B (P = 0.01). The probability of > or =2 grade a-GVHD was 19% (A) and 27% (B) (P = 0.53). The probability of all grade c-GVHD was 70% with BM. In spite of the small number of patients in group B (PBPC), our data suggest the great majority of them will have c-GVHD (P = 0.08); extensive disease was present in 50 and 100%, respectively (P = 0.05). The estimates of overall survival for A and B at 1000 days are 51 and 47%, respectively (P = 0.67); DFS at 1000 days are 52 and 58%, respectively (P = 0.50). PBPC resulted in faster platelet engraftment. The incidence of acute and chronic GVHD was similar in both groups, but the severity of c-GVHD was higher with PBPC. No differences in survival and DFS have been observed to date.
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PMID:A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies. 989 16

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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PMID:Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study. 1045 58

13 patients have been transplanted at Institute of Hematology and Blood Transfusion since 1995 using allogeneic PBPC either alone or with bone marrow as a source of progenitor cells. All donors were G-CSF mobilised HLA identical family members. PBPC harvests were performed on D 4,5, (6) of G-CSF administration. The medium content of TNC, CD34+, CD3+, CD4+and CD8+cells/kg b.w. of the recipients in the grafts were: 13,1x10(8)(TNC), 11,4x10(6)(CD34+), 393x10(6)(CD3+) 243x10(6)(CD4+), 125x10(6)(CD8+) The patients received either BuCy2 or CyTBI preparative regimen and Cyclosporin A + short course of Methotrexate for GVHD prophylaxis. Engraftment of ANC >500 was achieved by D+16 and PLT >20.000 by D+19. Three of ten evaluable patients developed acute and three of nine chronic GVHD. 8 patients survive with the longest follow up 776 days.
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PMID:Transplantation of allogeneic peripheral blood progenitor cells--a single centre experience. 991 42

We report three acute myelogenous leukemia (AML) patients who developed intracerebral granulocytic sarcomas (GS) and were successfully treated with allogeneic BMT (allo-BMT). The diagnosis of one patient was AML M2 with myelofibrosis, and the other two patients were AML M4 with eosinophilia (AML M4 Eo), according to the FAB classification. Two patients first experienced a relapse in the brain that resulted in the formation of GS, followed by a relapse in the bone marrow. The remaining patient developed an optic nerve GS after suffering a bone marrow relapse. All three patients received irradiation for the GS and systemic chemotherapy before the allo-BMT. TBI was used for conditioning, and GVHD prophylaxis was with cyclosporine (CsA) and short-term MTX in all three cases. These patients are currently 9 to 37 months post-BMT without relapse. Thus, our experience suggests that allo-BMT is an effective treatment for AML patients with existing or pre-existing intracerebral GS.
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PMID:Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations. 1067 89

Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n = 26; CML n = 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P = 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P = 0.44). Patients younger than 40 years (n = 33) had a similar TRM as patients 40 years and older (n = 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P<0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.
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PMID:Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia. 1023 Nov 35

Unmodified allogeneic peripheral blood stem cell transplantation (alloPBSCT) was performed in 20 consecutive acute non-lymphoblastic leukemia (ANLL) patients from their HLA-identical siblings. There were 11 males and 9 females. Median age was 34 years (range 17-43). Donors were primed with 2.5-15 micrograms/kg/day s.c. granulocyte-colony stimulating factor (G-CSF, Neupogen, Roche). Conditioning regimen was Bu (16 mg/kg) + Cy (120 mg/kg) in 19 patients and high dose Ara-C (3 gr/m2 twice daily for 3 days) for one patient who relapsed after bone marrow transplantation. Eighteen patients were in CR1. CsA + short-term MTX (n = 19) or CsA alone (n = 1) were used for graft versus host disease (GVHD) prophylaxis. The median number of apheresis procedures for each patient was 2 (2-4). A median of 6.5 (3.2-38.2) x 10(8)/kg MNC or 9.4 (2.2-12.4) x 10(6)/kg CD34+ cells were given. Median days to reach granulocyte of > 0.5 x 10(9)/l and platelet of > 50 x 10(9)/l were 12 (10-14) and 15 (11-35) respectively. Day 100 transplant-related mortality was 20 per cent (4/20). Grade 2 to 4 AGVHD was seen in 8 out of 17 (47%) evaluable patients. Severe AGVHD occurred in 3 out of 17 (18%). Clinical CGVHD of all grades developed in 12 out of 17 (70%) evaluable patients. The mean disease-free survival and overall survival were 17 (range: 8-33 months) and 18 months (range: 10-34 months), respectively. In conclusion, alloPBSCT in ANLL is associated with a faster engraftment, no greater incidence of AGVHD, but increased risk of CGVHD.
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PMID:Allogeneic peripheral blood stem cell transplantation in acute non-lymphoblastic leukemia. 1041 35

Bone marrow transplant (BMT) recipients are prone to bacterial, viral and fungal infections. Mycobacterium tuberculosis infection can occur in these patients, but the incidence is lower than that of other infections. This report describes four patients with Mycobacterium tuberculosis infection identified from 641 adult patients who received a BMT over a 12-year period (prevalence 0.6%). The pre-transplant diagnosis was AML in two patients and CML in the other two. Pre-transplant conditioning consisted of BU/CY in three patients and CY/TBI in one. Graft-versus-host disease (GVHD) prophylaxis was MTX/CsA in three patients and T cell depletion of the graft in one patient. Sites of infection were lung (two), spine (one) and central nervous system (one). Onset of infection ranged from 120 days to 20 months post BMT. Two patients had co-existing CMV infection. One patient had graft failure. The two patients who received anti-tuberculous (TB) therapy recovered from the infection. Although the incidence of tuberculosis in BMT patients is not as high as in patients with solid organ transplants, late diagnosis due to the slow growth of the bacterium can lead to delay in instituting anti-TB therapy. A high index of suspicion should be maintained, particularly in endemic areas.
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PMID:Mycobacterium tuberculosis infection in allogeneic bone marrow transplantation patients. 1048 41

Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.
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PMID:Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. 1051 80

A 24-year-old woman with CML underwent allogeneic BMT in August 1995 from a one-antigen HLA mismatched brother. Conditioning included BuCy2 and CsA and MTX were used to prevent GVHD. In July 1997 she developed right leg pain, lytic bone lesions of distal femur and a solid mass of soft tissue. Histological diagnosis of malignant fibrous histiocytoma was made. Despite treatment with surgery and chemotherapy (doxorubicin and ifosfamide), the patient died 1 year later with local recurrence of the tumor and liver, lung and brain metastases. The CML was in CR.
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PMID:Malignant fibrous histiocytoma after allogeneic bone marrow transplantation. 1055 64

To minimize immunosuppression, allow a graft-versus-leukemia (GVL) effect, and reduce relapse incidence, 73 leukemic recipients of human leukocyte antigens-identical sibling marrow were given graft-versus-host disease (GVHD) prophylaxis based on the estimated risk of GVHD development. Methotrexate (MTX) monotherapy was given to patients with an estimated low risk of developing GVHD, whereas MTX + cyclosporine (CsA) was given to 'high-risk' patients. After engraftment, CsA was discontinued, and weekly MTX was reinstituted and given until 3 months post-bone marrow transplant. Conditioning consisted of busulfan (BU) + cyclophosphamide (CY) (n = 35) or CY + total body irradiation (TBI) (n = 38). Retrospective controls were given CY + TBI and MTX + CsA (n = 39). The median observation time was 5 yr 11 months. Chronic GVHD increased to 53% in the individual BU + CY group and 46% in the individual CY + TBI group, compared to 25% in the control group (p = 0.05). This increase was restricted to the limited form. The actuarial relapse incidence decreased to 20% in the individual BU + CY group, compared to 52% in the control group, p = 0.03. In the individual CY + TBI group, the relapse incidence was 44% (n.s. versus controls, p = 0.04 versus individual BU + CY). The 5-yr relapse-free survival (RFS) in the individual BU + CY group was 66%, in the control group, 41% (p = 0.07), and in the individual CY + TBI group, 45% (p = 0.1 versus individual BU + CY). Patients with early leukemia in the individual BU + CY group had a RFS of 83%, compared to 44% in the control group (p = 0.02) and 42% in the individual CY + TBI group (p = 0.01). In the multivariate analysis, advanced leukemia beyond first complete remission and first chronic phase and conditioning with CY + TBI were correlated to poor RFS. In summary, the individualized prophylaxis itself did not reduce the relapse incidence. However, in patients with early leukemia conditioning with BU + CY, our method of individualizing the GVHD prophylaxis might be of value, since this group had the best RFS in this study.
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PMID:Improved survival after bone marrow transplantation for early leukemia using busulfan-cyclophosphamide and individualized prophylaxis against graft-versus-host disease: a long-term follow-up. 1061 42


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