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)

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.
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PMID:[Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia]. 1644 Jul 47

This study attempts to identify variables that can predict the development of progressive- or quiescent-type chronic GVHD (pq cGVHD) and transplant outcomes after the diagnosis of cGVHD in 99 patients who experienced acute GVHD (aGVHD) after allogeneic SCT. The prognostic significance of various clinical parameters at diagnosis of cGVHD was examined to determine the prognostic factors for GVHD-specific survival (GSS) in patients with pq cGVHD. Among 118 patients who experienced any degree of aGVHD, 99 were evaluated for cGVHD. The incidence of overall and extensive pq cGVHD at 2 years was estimated as 84.4 and 63.1%, respectively. A multivariate analysis showed that severe aGVHD (grade 3, 4) (P=0.022), primary treatment failure (P=0.009) and elevated alkaline phosphatase (P=0.001) were all significant independent factors predicting a higher overall incidence of pq cGVHD. The GSS and probability of systemic immunosuppressive treatment at 2 years after diagnosis of cGVHD were estimated as 55.9 and 51.9%. GVHD-specific survival was significantly associated with performance status (P=0.004) and lymphocytopenia (<or=1000/microl, P=0.022) at diagnosis of cGVHD by Cox's proportional hazard model. Severe aGVHD, primary treatment failure (PTF), lymphocytopenia and elevated alkaline phosphatase may be useful predictive factors for the development of pq cGVHD in patients who experience aGVHD after allogeneic SCT.
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PMID:Risk-factor analysis for predicting progressive- or quiescent-type chronic graft-versus-host disease in a patient cohort with a history of acute graft-versus-host disease after allogeneic stem cell transplantation. 1650 88

GVHD is a major complication after allogeneic SCT. Etiology of GVHD is multifactorial. Known role of hSPS in antigen presentation could suggest their potential role in the alloreactive process that leads to aGVHD. HSPS represent major immunodominant antigens in a wide spectrum of microbial pathogens. Bacterial and fungal colonization, infection and sepsis are frequent in immunocompromised patients with various malignant and non-malignant diseases. We studied PBMC responses to recombinant human hsp60 (rh-hsp60), rh-hsp70 and Mycobacterium bovis hsp65 (M. bovis hsp65) in relation to aGVHD and infection in 34 pediatric patients with various lympho-hemopoietic malignancies as well as non-malignant disorders subjected to SCT. PBMC of patients before initiation of preparative regimen as well as after engraftment were stimulated with hSPS (1 microg/mL/well, 7-day cultivation). PHA was used as a control of the stimulation ability. Cell responses were measured after the incorporation of 3H-thymidin (pulsing with 1 microCi/well) and were expressed as stimulation indexes (SI). We demonstrated significantly high proliferative response to rh-hsp60 as well as M. bovis hsp65 in a cohort of pretransplant patients with anamnestic and/or actual infection when compared with a cohort of patients without infection and healthy individuals. Strong PBMC cell responses to hSPS were found in patients who were at present colonized with Escherichia coli and Klebsiella pneumoniae or had previously K. pneumoniae infection with subsequent sepsis. Our findings support various studies dealing with immunodominant hSPS in connection with several pathogens and infectious diseases. Although no statistical difference for proliferative response to PHA was observed, PBMC responses against all tested hSPS comparing a cohort of patients with aGVHD and that with no sign of GVHD resulted in significantly lower SI for all tested hSPS in patients with aGVHD. Lower stimulation with hSPS during aGVHD might be explained by the stress-induced upregulation of self-hSPS synthesis that might lead to the inhibition of self-hSPS reactive T-cell response. Vice versa, we hypothesize that increased hsp-specific stimulation may reflect the presence of protecting regulatory T cells preventing the development of Th1-mediated diseases involving aGVHD.
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PMID:Peripheral blood mononuclear cell responses to heat shock proteins in patients undergoing stem cell transplantation. 1657 4

We describe a patient with Wegener granulomatosis (WG) who underwent long-term cyclophosphamide treatment and thereafter developed acute myelogenous leukemia (AML). After the AML was induced into remission, the patient received an allogeneic stem cell transplant (allo-SCT) from his sibling after undergoing a reduced-intensity conditioning regimen. His clinical course shortly after allo-SCT was uneventful. No clinically apparent acute or chronic graft-versus-host disease developed. Repeated analysis of the peripheral blood lymphocytes after transplantation showed complete donor chimerism. The level of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) remained undetectable until 4 months after transplantation, when it began to increase. When the level of PR3-ANCA peaked, the patient suddenly presented with fever and joint pain, which later spontaneously resolved in parallel with the declining titer of PR3-ANCA. He is now in remission for both AML and WG at 22 months after transplantation. The patient's clinical course after allo-SCT may provide us with valuable information regarding the establishment of allo-SCT as a therapeutic option for WG.
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PMID:Bone marrow transplantation with a reduced-intensity conditioning regimen in a patient with Wegener granulomatosis and therapy-related leukemia. 1672 May 60

This study investigated whether or not there is a correlation between the changes in the serum levels of vascular endothelial growth factor (VEGF) and the outcome of allogeneic stem cell transplantation (allo-SCT). Eighty-five patients undergoing allo-SCT were prospectively studied. The serum VEGF levels were measured on days 0, +7 and +14 after transplantation. The VEGF levels decreased significantly on day +7 and recovered on day +14. The highest levels from day +7 through day +14 were categorized by cluster analysis, which were then correlated with the nonrelapse mortality (NRM). There was a significant correlation between a low VEGF level and the occurrence of severe acute graft-versus-host disease (GVHD) including grade III-IV (P=0.029). The 1-year probability of NRM in patients with a low VEGF level was 22.5% compared with 3.5% for those with a high VEGF level (P=0.024). Multivariate analysis revealed clinically defined infections (P=0.011), advanced disease (P=0.014) and a low VEGF cluster (P=0.05) to be significantly associated with the occurrence of NRM in the cohort. In conclusion, low VEGF levels after allo-SCT are associated with NRM with an exacerbated severity of acute GVHD. VEGF monitoring after a transplant might identify those patients at risk of severe transplant-related mortality.
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PMID:Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation. 1675 84

In this retrospective study, we evaluated donor lymphocyte infusions given for relapsed (n=48) or persistent (n=15) myeloma following non-myeloablative allogeneic stem cell transplantation (Allo-SCT). Twenty-four of 63 patients (38.1%) responded: 12 patients (19.0%) with a partial response (PR) and 12 patients (19.0%) with a complete response (CR). Overall survival after donor lymphocyte infusions (DLI) was 23.6 months (1.0-50.7+). Median overall survival for non-responding patients was 23.6 months and has not been reached for the patients responding to DLI. In responders, progression-free survival after DLI was 27.8 months (1.2-46.2+). Patients with a PR had a median progression-free survival of 7.0 months, whereas patients with a CR to DLI had a median progression-free survival of 27.8 months. Major toxicities were acute graft-versus-host disease (GVHD) (38.1%) and chronic GVHD (42.9%). Seven patients (11.1%) died from treatment-related mortality. The only significant prognostic factors for response to DLI were the occurrence of acute and chronic GVHD. There was a trend towards significance for time between transplantation and DLI, and response. Donor lymphocyte infusion following non-myeloablative Allo-SCT is a valuable strategy for relapsed or persistent disease.
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PMID:Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma. 2097 68

The indication for allogeneic stem cell transplantation (allo-SCT) have been expanded nowadays because many stem cell sources became available and new conditioning procedures such as reduced intensity stem cell transplantation (RIST) have been developed. Stem cell sources can be classified into bone marrow cells, peripheral blood stem cells, cord blood cells and every source derived from related or unrelated donors. Also, HLA mismatched transplantation has been studied especially in haploidentical donors. Now we must select the most compatible stem cell source for the recipient condition and disease status. RIST has expanded the indication of allo-SCT because of low regimen related toxicity. However, evaluation of graft versus leukemia (GVL) effect and control of graft versus host disease (GVHD) are still unresolved problems. Further investigations of the therapy of chronic GVHD and other posttransplant problems are warranted to improve the outcome and quality of life of the patients.
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PMID:[Recent progress in hematopoietic stem cell transplantation]. 1677 89

A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg . m(-2) . d(-1) on day (d) -7 through d -3 and cyclophosphamide 60 mg . kg(-1) . d(-1) on d -4 and d -3. Patients received 2-8 x 10(6) CD34+ cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC.
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PMID:Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study. 1722 50

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.
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PMID:Successful treatment of minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia with imatinib followed by reduced-intensity unrelated cord blood transplantation after allogeneic peripheral blood stem cell transplantation. 1692 41

One of the most frequent consequences of allogeneic haemopoietic stem cell transplantation (allo-SCT) in both males and females is gonadal insufficiency. We report the case of a 27-year-old myelodysplastic male who developed azoospermia after allogeneic transplantation of haemopoietic stem cells from his HLA-identical sister. Post-transplant azoospermia was alternated with intermittent severe oligospermia. The patient had a normal endocrine pattern and evidence of mild chronic graft-versus-host disease (cGVHD). Normal intratesticular spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology. Inflammation was evident at semen analysis, but no infection was detected by microbiological examination and sperm culture. These findings, together with the re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive treatment, suggested the presence of cGVHD of the urogenital tract, causing a reversible obstruction of the spermatic tract and cryptozoospermia. This is the first case report documenting a severe impairment of sperm count because of a reversible obstruction of the seminal tract, likely caused by cGVHD, in a long-term survivor of allo-SCT with normal endocrine pattern. An important practical consequence of this case report is the fact that azoospermia was cured using low-dose immunosuppressive therapy, and this allowed us to avoid expensive stimulatory treatments with gonadotrophins, which remain, however, ineffective if the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated pregnancy occurred in the partner of the patient 3 months after the corticosteroid treatment withdrawal.
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PMID:Cryptozoospermia with normal testicular function after allogeneic stem cell transplantation: a case report. 1700 Jun 49


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