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)

Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen.
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PMID:Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes. 847 79

Procollagen-III peptide (PIIIP) has been suggested as a marker for hepatic veno-occlusive disease (VOD) after bone marrow transplantation (BMT). Using the RIA-gnost PIIIP assay, we examined frozen plasma samples from three groups of patients. The groups included (A) four patients with clinically proven VOD, (B) nine patients with remarkably uneventful post-BMT courses, and (C) patients with either early complications other than VOD or pulmonary fibrosis in their later course. In group A, PIIIP levels increased parallel to the clinical course, with maximum values of 2.7-5.5 units/ml. In group B, values did not exceed 1.4 units/ml. In group C, higher values were occasionally observed. In one patient with early relapse of a lymphoma PIIIP peaks correlated with episodes of fever and graft versus host disease (GVHD). In another patient mild VOD seems possible retrospectively. The highest levels ( > 15 units/ml) occurred in one patient with ileus. Several patients with interstitial pneumonia (IP), adult respiratory distress syndrome (ARDS), or lung fibrosis showed increases in PIIIP levels corresponding to the clinical course; most of these events occurred later than day 30 after BMT. One patient with severe GVHD of the liver showed a maximum of only 1.4 units/ml. PIIIP elevation correlated with clinical VOD and may help to differentiate it from hepatic GVHD. In the presence of other complications (pulmonary, gastrointestinal), some caution in interpreting the results may be advisable.
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PMID:Evaluation of procollagen-III peptide as a marker for veno-occlusive disease after bone marrow transplantation. 869 19

Hepatic dysfunction is common in patients who receive intensive chemotherapy and it is important to determine the etiology in order to institute appropriate therapy. The role of laparoscopic liver biopsy in patients with neutropenia, thrombocytopenia, or both was evaluated as a mean of making treatment decisions and as a determinant of clinical outcome. Laparoscopic liver biopsy was performed in 29 subjects who were receiving intensive cytotoxic therapy with or without bone marrow transplantation. One to three direct-vision laparoscopic liver biopsies were performed in each patient using a Tru-cut needle during general anesthesia. Platelet concentrate transfusions were usually given before, during, and immediately after biopsy. Bleeding was controlled with spatula electrocautery. Thirty-two biopsies were obtained in 29 patients. At the time of liver biopsy, white blood cell and platelet counts ranged from 0 to 14,300/microliters (median: 2500/microliters), and 1000 to 47,000/microliters (median: 20,000/microliters), respectively. Bleeding at the liver biopsy site was readily controlled during the procedure without clinical evidence of significant bleeding; no procedure-related complications were noted and no patients required re-exploration. All biopsies were informative and the lesions observed in 32 biopsies revealed graft-versus-host disease (n = 5), hepatic candidiasis (n =1), hepatic veno-occlusive disease (n = 3), cholestasis (n = 19), hemosiderosis (n = 26), toxic injury (n = 8), hepatic steatosis (n = 4), granuloma (n = 1), viral infection (n =1), and malignancy (n = 1). Laparoscopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients who were thrombocytopenic and immunosuppressed. The diagnosis obtained at laparoscopic liver biopsy altered therapy in nine of 29 (31%) patients.
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PMID:Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management. 872 71

Although hepatic veno-occlusive disease (HVOD) is a common complication of allogenic bone marrow transplantation (BMT), pulmonary veno-occlusive disease (PVOD) is very rare. Only three cases have been described in the literature. We report the case of a 19-year-old woman who developed PVOD accompanied by microangiopathic hemolytic anemia (MAHA) and hemolytic uremic syndrome (HUS) 1 year after a second BMT for relapsed acute lymphoblastic leukemia (ALL). Autopsy examination revealed obstruction of the small pulmonary veins with edematous thickening of the intima. These findings are compatible with PVOD. Pulmonary GVHD and pulmonary aspergillosis were also observed. Various etiologic factors have been implicated in PVOD after BMT. We postulate that pulmonary GVHD and pulmonary infection including aspergillosis played an important role in the occurrence of both PVOD and HUS in our patient. Microangiopathic cytokines released in response to the GVHD and infection may damage the intima of microvessels that were previously injured by the two BMT. Despite appropriate therapy, the microangiopathic process was irreversible and the patient died. Thus, measures must be taken to prevent and treat PVOD after BMT.
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PMID:Pulmonary veno-occlusive disease accompanied by microangiopathic hemolytic anemia 1 year after a second bone marrow transplantation for acute lymphoblastic leukemia. 885 72

Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocytes and platelets. An ELISA was developed for measuring TPO concentrations in human sera. The mean +/- S.D. of TPO level obtained in 29 control subjects was 0.87 +/- 0.35 fmol/ml. We measured the TPO level in 36 patients after allogeneic bone marrow transplantation (BMT) and determined the relationship between blood levels of TPO and changes in the circulating platelet mass. In general, a reciprocal relationship was observed between TPO and platelet count (r = -0.609, P < 0.0001; n = 165). With the decrease in the platelet mass after myeloablative therapy, the TPO level increased proportionally and peaked during the platelet nadir. The peak concentration of TPO ranged from 20-50 fmol/ml. The TPO level decreased with the normalization of the platelet mass. In contrast, the TPO level decreased during acute graft-versus-host disease (GVHD) in several patients. Furthermore, the TPO level was significantly lower in the patients with hepatic veno-occlusive disease (VOD) than in the patients after BMT without GVHD and VOD in the samples of less than 50000/microliters platelets (P < 0.005). These findings suggest that in the patients given allogeneic BMT, TPO has an important role in the physiologic regulation of platelet production and that liver damage due to acute GVHD and VOD may decrease the TPO level.
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PMID:Serum thrombopoietin level after allogeneic bone marrow transplantation: possible correlations with platelet recovery, acute graft-versus-host disease and hepatic veno-occlusive disease. Nagoya Bone Marrow Transplantation Group. 892 86

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean +/- SD) was significantly (P < .001) elevated in patients with VOD (321.6 +/- 161.2 ng/mL) as compared with patients with GVHD (22.8 +/- 8.4 ng/mL) or other hepatic damage (32.8 +/- 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 +/- 230.0 ng/mL in patients with VOD, 41.0 +/- 20.6 ng/ mL in patients with GVHD, and 44.6 +/- 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.
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PMID:Plasminogen activator inhibitor-1 confirms the diagnosis of hepatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation. 905 43

We have previously demonstrated that syngeneic marrow mixed with H-2 haploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observations using autologous marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthemia (42.5 degrees C for 70 min) following incubation for 5 days with interleukin 2 (IL-2) in liquid culture and mixed with HLA haploidentical marrow cells from their sibling or parent. Acute GVHD was not observed in any patient after transplantation. Hematological rescue in the clinical setting was demonstrated in all cases but one who died early from hepatic veno-occlusive disease (VOD). Five cases who were transplanted at the time of CR2 or CR3 and in advanced phase of lymphoma, relapsed 4 to 7 months after transplantation. The relapse rate was 31.3%. None of eight patients who received allogeneic BMT within 2 h after ABMT relapsed with median follow-up of 12 months and two of them died from procedure-related complications. Seven cases are still alive and disease-free with a median follow-up of 12 months. Mixed chimerism was found in 3/6 cases, who had different sex donors, by analysis of sex chromosomes. These results show that mixed transplantation is a safe, effective and new approach to treating patients with malignant tumors. In order to detect the effects of GVL, studies are now in progress in our clinic.
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PMID:Autologous bone marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. 911 6

Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18-58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.
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PMID:Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation. 925 90

In this review we examine the clinical outcomes of patients who have received both bone marrow transplantation (BMT) and solid organ transplantation (SOT) and discuss the possible immunologic consequences of the dual transplants. We collected cases through a comprehensive literature search (MEDLINE database, English literature only) covering the years 1990 through 1997 and correspondence with the International Bone Marrow Transplant Registry. Our study selected case reports of patients who have undergone both bone marrow and solid organ transplants; cases in which bone marrow transplantation was undertaken as an adjunct ot induce or augment donor-specific tolerance in a recipient to the transplanted organ were excluded. Clinical characteristics included patient's demographic information, underlying disorders for each transplant, source of donor organ or tissue, time between transplants, and immunosuppressive regimens used to prevent graft-versus-host disease (GVHD) or graft rejection. Clinical outcomes included patient survival, complications of transplantation, and donor-specific tolerance that was experienced in many cases. Twenty-one cases of SOT after BMT and 7 cases of BMT after SOT were reviewed. Solid organ transplantations included lung, liver, cardiac, and kidney for a variety of BMT-related complications including GVHD, hepatic veno-occlusive disease, chronic renal failure, end-stage pulmonary disease, and severe cardiomyopathy. Bone marrow transplants were performed following SOT for aplastic anemia and hematologic malignancies. Clinical outcomes for patients who received both BMT and SOT were variable and depended on transplant indication and degree of histocompatibility. Prior bone marrow transplantation may tolerize for a subsequent organ transplant from the same donor. Conversely, severe GVHD may follow BMT from human leukocyte antigen (HLA)-matched donors following SOT. The favorable survival in this high-risk group of patients may represent a literature review bias (that is, an undetermined number of unsuccessful cases may not have been reported). Nonetheless, dual transplantation is clearly feasible in selected cases.
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PMID:Outcomes of recipients of both bone marrow and solid organ transplants. A review. 977 24

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in five, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24.5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome.
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PMID:Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients. 1052 13


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