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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)

Engraftment syndrome, autologous graft-versus-host disease (GVHD), and infection after autologous hematopoietic cell transplantation can have similar clinical presentations. Here, we describe a patient with refractory Ewing sarcoma who had recurrent skin rash after autologous hematopoietic cell transplantation. Although the rash was diagnosed as GVHD histologically, this case illustrates the diagnostic dilemma of distinguishing engraftment syndrome, autologous GVHD, or concomitant viral infection. Because therapy for these entities is different, distinguishing them is important. Establishment of diagnostic criteria and understanding of the pathophysiology of these entities may lead to better management and to improved therapy of refractory cancer.
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PMID:Diagnostic challenge in recurrent skin rash after autologous bone marrow transplantation. 1691 92

Denileukin diftitox (Ontak) was evaluated in combination with methotrexate (MTX) for preventing acute graft-versus-host disease (GVHD) in dogs given 9.2 Gy of total body irradiation and DLA-nonidentical hematopoietic cell grafts. Six dogs were given denileukin diftitox 9 ,microg/kg/day intravenously (IV) on days 2, 4, 5, 7, 8, and 10, in combination with MTX 0.4 mg/kg/day IV on days 1, 3, 6, and 11 after transplantation. Median survival of the dogs given MTX in combination with denileukin diftitox was 16 days (range, 13-18 days), similar to that of 35 historical controls given MTX alone (median survival, 20 days). Five of the 6 denileukin diftitox-treated dogs had clinical and pathological evidence of 3-system GVHD; 1 dog died of canine herpes virus infection without evidence of GVHD. In conclusion, denileukin diftitox did not prevent, mitigate, or delay acute GVHD in this stringent and predictive (with respect to outcomes in human patients) hematopoietic cell transplantation model.
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PMID:Denileukin diftitox as prophylaxis against graft-versus-host disease in the canine hematopoietic cell transplantation model. 1692 May 55

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following myeloablative conditioning represents the treatment of choice for patients with chemotherapy-resistant leukemia. We describe a 49-year-old man with advanced, refractory acute myelogenous leukemia (AML) that was treated successfully by allogeneic bone marrow transplantation from a sibling donor with HLA mismatched at 1 locus. However, the patient developed a quiescent form of chronic graft-versus-host disease (GVHD) 7 years after transplantation, requiring long-term immunosuppressive therapy. AML relapse was documented 11 years after transplantation. Subsequently, Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD) was also diagnosed. Immune reconstitution after allo-HSCT might have been impaired by the persistent chronic GVHD and the prolonged administration of immunosuppressive agents. As a result, immune surveillance against remaining quiescent leukemic cells as well as viral infection may have been defective, leading to the relapse of leukemia and EBV-associated PTLD.
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PMID:Late relapse of acute myelogenous leukemia followed by epstein-barr virus-associated lymphoproliferative disease 11 years after allogeneic bone marrow transplantation. 1718 27

Acute and chronic liver disease contributes significantly to morbidity and mortality following hematopoietic cell transplantation (HCT). The best prognostic indicator for the development of severe liver dysfunction is an early rise in liver function test results after HCT. The leading causes soon after HCT are acute graft-versus-host disease (GVHD), sinusoidal obstruction syndrome, drug and total parenteral nutrition hepatotoxicity, sepsis, and viral infection. Hepatic herpesvirus and fungal infections after HCT, though uncommon, can be life-threatening and warrant immediate diagnosis and treatment. Hepatitis B, hepatitis C virus, iron overload, and chronic GVHD are among the most common causes for chronic liver disease after HCT. Because treatments are directed at the underlying etiology of liver disease, prompt diagnosis by means of laboratory tests, hepatic imaging, and often liver biopsy is required after HCT.
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PMID:Hepatic complications of hematopoietic cell transplantation. 1733 79

Immunosuppressive monoclonal antibodies directed to immune system cells may reduce rejection and graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT), but can increase the risks of viral infection. Here, we report human herpes virus-6 (HHV-6) encephalitis despite antiviral prophylaxis in 5 of 43 (11.6%) patients receiving alemtuzumab supported conditioning. Encephalitis occurred at 41-103 days (median 60 days) presenting with confusion in all patients, combined with amnesia (n=3) or seizures (n=2). MRI revealed non-specific white matter changes in two and a non-enhancing medial temporal lobe lesion in three patients. Cerebrospinal fluid (CSF) PCR amplification for HHV-6 was positive in all five patients, (600-2 25 000 (median 4700) copies/ml CSF), while analysis of peripheral blood revealed 100-22 500 (median 1200) viral copies/ml plasma. CSF protein was elevated in four patients, with minimal CSF pleocytosis. Intravenous foscarnet produced neurological improvement at 8-13 (median 11) days and negative plasma PCR at 30-66 (median 50) days. Four patients had complete neurological recovery, but one patient with persistent viral DNA in the CSF succumbed to progressive encephalopathy. Given this high incidence of HHV-6 and the possibility of successful outcome with prompt treatment, a high index of suspicion of this disorder is required in recipients of monoclonal antibody supported allografts.
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PMID:Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation. 1740 92

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%-50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.
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PMID:Acute graft versus host disease. 1778 64

In certain inborn errors of metabolism, an allogeneic stem cell transplantation is able to prevent disease progression. This is only possible when the stem cell transplantation (SCT) is performed early in life, before cerebral involvement has occurred. In addition to bone marrow and peripheral blood, unrelated umbilical cord blood appears to be an effective stem cell source as well. Important advantages of umbilical blood as stem cell source are: the time between diagnosis and SCT can be considerably reduced; there is a greater chance of finding a suitable donor and the risk of graft-versus-host disease and viral transmission is decreased. By far the most common disease in the group of inborn metabolic errors for which SCTs are performed is Hurler's disease. In these patients, the percentage of successful transplantations is considerably higher after the use ofunrelated cord blood than when bone marrow or peripheral blood is used as a stem cell source. In addition, donor chimerism occurred significantly more often in those patients who had received unrelated umbilical cord blood. There are also potential disadvantages attached to the use of umbilical blood as stem cell source: the possibility of only one donation per donor and less adaptive immunity following umbilical blood SCT with an increased risk of reactivation of a previous viral infection. However, these disadvantages are less applicable to young children with inborn errors of metabolism. The improvement of transplantation techniques and the availability of this new stem cell source could improve the success rate of this procedure and consequently the prognosis of these severely affected patients.
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PMID:[Umbilical cord blood from an unrelated donor as source for stem cell transplantations in inborn errors of metabolism]. 1872 2

This study was purposed to investigate immune reconstitution at 12 months after allogeneic peripheral blood stem cell transplantation (all-PBSCT) and its relation with the influencing factors such as age, HLA compatibility, graft versus host disease and viral infection. The T lymphocyte subgroups (CD3(+), CD4(+), CD8(+)), B lymphocyte (CD19(+)) and NK (CD16(+)CD56(+)) cells in peripheral blood and serum immunoglobulin concentrations (IgG, IgA and IgM) of 37 patients were analyzed by flow cytometry and scatter turbidimetry, respectively at 1, 3, 6 and 12 months after transplantation. The results showed that CD3(+) cell percentage was (47.5 +/- 23.2)% at 1 month, (75.1 +/- 6.4)% at 3 months, (69.7 +/- 12)% at 6 months and (71.7 +/- 4.2)% at 12 months. CD4(+) cell percentage was (13.3 +/- 6.4)% at 1 month, (20.2 +/- 11.4)% at 3 months, (46.9 +/- 10.3)% at 6 months and (29.1 +/- 18.7)% at 12 months. CD8(+) cell percentage was (43.1 +/- 23.2)% at 1 month, (42.6 +/- 16.9)% at 3 months, (69.7 +/- 12)% at 6 months and (47 +/- 5.6)% at 12 months. CD16(+)56(+) cell percentage was (14.4 +/- 8.4)% at 1 month, (15.9 +/- 7.6)% at 3 months, (14.7 +/- 6.6)% at 6 months and (13.6 +/- 3.4)% at 12 months. CD19(+) cell percentage was (6.4 +/- 5.6)% at 1 month, (11.7 +/- 2.4)% at 3 months, (13.3 +/- 7.3)% at 6 months and (16.7 +/- 5.7)% at 12 months. The serum concentration of IgA was (0.37 +/- 0.14) g/L at 1 month, (0.28 +/- 0.21) g/L at 3 months, (0.42 +/- 0.18) g/L at 6 months and (0.53 +/- 0.34) g/L at 12 months. The serum concentration of IgG was (12.7 +/- 3.8) g/L at 1 month, (16.3 +/- 5.2) g/L at 3 months, (14.3 +/- 6.2) g/L at 6 months and (15.4 +/- 6.9) g/L at 12 months. The serum concentration of IgM was (0.56 +/- 0.24) g/L at 1 month, (0.64 +/- 0.16) g/L at 3 months, (1.1 +/- 0.35) g/L at 6 months and (1.2 +/- 0.28) g/L at 12 months. There were no significant differences between percentage of T lymphocyte subgroups in peripheral blood and serum immunoglobulin concentrations of the patients > or = 45 years old and the patients < 45 years old. The CD19(+) cell percentage of the patients with chronic GVHD at 12 month was less than that of the other ones at 12 months after transplantation. CD4(+) and CD19(+) cell percentage recovery in the patients of haploidentical transplantation was later than that in patients of HLA complete identical transplantation. The CD4(+)/CD8(+) cell ratio and CD4(+) cell percentage of those patients infected with herpes zoster were significantly lower than those without herpes zoster. It is concluded that the CD3(+) cell percentage begins to recover at 3 months after allo-PBSCT. CD4(+) cell percentage begins to recover at 6 months after allo-PBSCT. CD8(+) cell percentage begins to recover at 1 month after allo-PBSCT. B cell percentage recovers at 3 to 6 months after allo-PBSCT. NK cell percentage recovers at 1 to 3 months after allo-PBSCT. The serum concentration of IgG recovers to normal at 1 month after transplantation which is associated with routine infusion of immunoglobulin. The concentration of IgM gradually recovers to normal at 3 months after transplantation. The concentration of IgA does not recover to normal at 12 months after transplantation. The function of B cells recovers slowly in patients with cGVHD. The CD4(+) cell absolute value and CD4(+)/CD8(+) ratio significantly decrease in patients with herpes zoster.
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PMID:[Immune reconstitution after allogeneic peripheral blood stem cell transplantation]. 1892 11

HLA-matched sibling donor (MSD) stem cell transplantation can cure>60% of pediatric patients with acute lymphoblastic leukemia (ALL), but <30% of patients will have a sibling donor. Alternative donor (AD) transplantation can be curative but has a higher risk of graft-versus-host disease (GVHD). The addition of alemtuzumab (Campath 1-H) to AD transplants produces in vivo T cell depletion, which may reduce the risk for GVHD. We now report the outcome for 83 children with ALL (41 MSD, 42 AD) undergoing stem cell transplantation in first or second complete remission. All patients received myeloablative conditioning, including cyclophosphamide, cytarabine arabinoside, and total-body irradiation, with alemtuzumab administered to AD recipients. GVHD prophylaxis consisted of a calcineurin inhibitor with either short-course methotrexate or prednisone. Disease-free survival (DFS) for MSD recipients was 72.3% (95% confidence interval [CI], 55.4%-83.6%) versus 62.4% (95% CI, 45.2%-75.4%) for AD recipients. The 100-day mortality was 7.1% in the AD group and 2.4% in the MSD group. Relapse rates were identical (24%). Treatment-related mortality, principally viral infection, explained the difference in survival. For children undergoing stem cell transplantation (SCT) from alternative donors, alemtuzumab with a myeloablative conditioning regimen resulted in DFS comparable to MSD.
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PMID:Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. 1894 Jun 79

Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation is increasingly considered for patients with chronic lymphocytic leukemia (CLL). To investigate the impact of in vivo T cell depletion with alemtuzumab on the incidence of graft-versus-host disease (GVHD), nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), we retrospectively analyzed the outcomes of 62 consecutive CLL patients conditioned with fludarabine and melphalan at 4 institutions. For GVHD prophylaxis, 41 patients (cohort 1) received alemtuzumab and cyclosporin; and 21 patients (cohort 2) received cyclosporin plus methotrexate or mycophenolate. Donors were 50 siblings and 12 unrelated volunteers. Twenty-two (36%) patients received donor lymphocyte infusions (DLI), 20 (49%) from cohort 1 and 2 (10%) from cohort 2 (P=.002). Grade III-IV acute GVHD (aGVHD) was observed in 20% and 38% of patients from cohorts 1 and 2, respectively (P=.14). Extensive chronic GVHD (cGVHD) was observed in 10% and 48% of patients from cohorts 1 and 2, respectively (P=.03). There was a trend toward a higher viral infection rate in cohort 1 compared to cohort 2 (68% versus 43%, P=.062), but the incidence of cytomegalovirus (CMV) reactivation was not significantly different. The 3-year OS, PFS, NRM, and relapse rates were 65%, 39%, 28%, and 32%, respectively, for cohort 1; and 57%, 47%, 34%, and 20%, respectively, for cohort 2 (P=.629, P=.361, P=.735, and P=0.112, respectively). In conclusion, both methods of GVHD prophylaxis were equivalent in terms of survival. The administration of alemtuzumab led to reduced cGVHD, possibly improving quality of life.
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PMID:The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. 1928 41


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