BACKGROUND: Chronic graft-versus-host disease(GVHD) is a major cause of morbidity and mortality in long-term survivors of bone marrow transplantation, an increasingly used therapeutic option for hematological disorders. Cutaneous manifestations are frequently the presenting feature; therefore, the dermatologist needs to be aware of the wide spectrum of chronic cutaneous GVHD, enabling early diagnosis and management. OBJECTIVE: We investigated the clinical and histological features of chronic cutaneous GVHD in recipients receiving allogenic BMT. METHODS: On the basis of the patients' charts, photographs and biopsy specimens, we investigated the occurring interval, clinical manifestations and histological characteristics of chronic cutaneous GVHD in 37 patients from January 1, 1996 through December 31, 2000. RESULTS AND CONCLUSION: 1. The chronic cutaneous GVHD was preceded by the acute form of GVHD in 56.7% of patients, and occurred as an extension(18.9%) of acute GVHD, after a disease-free interval(37.8%), or with no precedent(43.2%). The disease usually developed at a mean 251days after transplant. 2. The chronic cutaneous GVHD mainly presented as maculopapular(37.8%), lichenoid(37.8%), or sclerodermoid(13.5%) patterns. 3. Histologically, 35.1% of biopsy specimens showed characteristic acute GVHR-like change, 40.5% showed lichen planus-like, and 13.5% was scleroderma-like histology. Lichen planus-like feature mixed with scleroderma-like was 2.7%, and 8.1 % was non-specific. 4. Appearing after day 100, the acute GVHD other than chronic GVHD was detected in some cases, and the lichenoid rash of chronic GVHD in one case was observed as early as day 60. 6. Our opinions are that the time of occurrence is not a reliable parameter for the clinical picture of GVHD and histologic parameters do not absolutely separate between acute and chronic GVHD as defined by days after BMT. 7. Mortality rate was 21 % in our cases.
Biopsy ; Bone Marrow Transplantation ; Early Diagnosis ; Exanthema ; Graft vs Host Disease* ; Humans ; Lichens ; Mortality ; Survivors ; Transplants*

Chemotherapy-induced acral erythema (CIAE) is a toxic reaction to a number of different chemotherapeutic agents, and causes symmetrical, well-demarcated, painful erythema on the palms and soles which is self-limiting. CIAE with bullous reaction in relation to methotrexate has been reported, but it is more commonly associated with cytosine arabinoside. The differential diagnosis of this condition from more serious conditions such as graft-vs-host disease or toxic epidermal necrolysis is essential. In this paper, we report the case of a 65-year-old man who developed bullous acral erythema after the administration of high-dose methotrexate for the treatment of Non-Hodgkin's lymphoma.
Aged ; Cytarabine ; Diagnosis, Differential ; Erythema* ; Graft vs Host Disease ; Hand-Foot Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Methotrexate ; Stevens-Johnson Syndrome

Hepatic graft-versus-host disease (GVHD) occurs in nearly one-third of recipients of HLA-identical sibling bone marrow transplantation (BMT), and is a major cause of morbidity and mortality following BMT. Hepatic dysfunction after BMT may result from a number of causes such as pretransplant chemoradiation, drugs for GVHD prophylaxis, venoocclusive disease, various infections, GVHD, and infiltration of recurrent malignancy. The clinical distinction of these causes may be difficult and the treatment of each causes is quite different. Therefore the early diagnosis of GVHD is very important. Hepatic GVHD is recognized to immunologic disorder such as primary biliary cirrhosis, and is characterized by cholestasis due to extensive bile duct damage and mild hepatocellular necrosis. In Korea, the occurrence of GVHD is about 20-45%. We report three cases of severe hepatic GVHD after allogeneic BMT, which were proven by laparoscopic liver biopsy in 1996. There were differences in primary illness, associated condition and disease progression.
Bile Ducts ; Biopsy* ; Bone Marrow Transplantation ; Cholestasis ; Disease Progression ; Early Diagnosis ; Graft vs Host Disease* ; Humans ; Korea ; Laparoscopy ; Liver Cirrhosis, Biliary ; Liver* ; Mortality ; Necrosis ; Siblings

BACKGROUND: Immune hemolysis secondary to ABO minor incompatibility is a rare graft versus host disease in renal recipients, secondary to anti-ABO antibody produced by lymphocytes of donor origin that reacts against recipient RBCs. METHODS: To investigate the incidence and clinical features of immune hemolysis secondary to ABO minor incompatibility in renal allograft recipients, clinical records of 358 renal transplantation performed in Maryknoll Hospital since 1991 were analyzed retrospectively. RESULTS: Fifty four (15%) of 358 renal transplants were ABO minor incompatible. Immune hemolysis secondary to anti-ABO antibody developed in 5 (9.2%) of 54 ABO minor incompatible renal transplant recipients. Immune hemolysis occurred in 3 (13.6%) patients among 22 allografts from blood type O donor to A recipients and 2 (10%) patients among 20 from blood type O donor to B recipients. All 5 patients received cyclosporin with prednisolone, and MMF was administered to one patient additionally. Immune hemolysis developed on 14+/-3 days after renal transplantation and lasted for about 10+/-3 days. The maximum reduction of hemoglobin was 3.3+/-1.0 g/dL. All patients required donor type (blood type O) washed RBCs transfusion (5.0+/-2.6 units per patient) and plasmapheresis were performed in 3 patients (4.0+/-1.0 per patient). All patients recovered without deterioration of graft function. Age, number of HLA mismatch, creatinine at 1 year after transplantation, frequency of acute rejection and serum cyclosporin level during first 2 weeks were not significantly different between hemolysis group (N=5) and non-hemolysis group (N=49). Living unrelated transplantation is associated with increased incidence of immune hemolysis compared with living related transplantation (p<0.01). CONCLUSION: Although immune hemolysis secondary to ABO minor incompatibility is uncommon, we experienced cases with marked reduction of hemoglobin that required a large amount of transfusion. Therefore, this type of immune hemolysis needs to be considered as a differential diagnosis of posttransplant hemolysis. As our center routinely performs donor specific transfusion (DST), the incidence may be higher than that of other centers where DST is not usually given.
Allografts ; Anemia, Hemolytic* ; Blood Group Incompatibility ; Creatinine ; Cyclosporine ; Diagnosis, Differential ; Graft vs Host Disease ; Hemolysis ; Humans ; Incidence ; Kidney Transplantation ; Lymphocytes ; Plasmapheresis ; Prednisolone ; Retrospective Studies ; Tissue Donors ; Transplantation ; Transplants

We experienced a case of cerebral hypoperfusion due to cyclosporine neurotoxocity confirmed only by Tc-99m ECD brain SPECT. A 53-year-old female had received allogenic peripheral blood stem cell transplantation due to refractory plasmacytoid lymphoma. Cyclosporine and steroid had been administrated to prevent graft versus host disease. Twenty days after transplantation, she became delirious and suffered from generalized tonic-clonic seizure. Immediately, brain MRI and MR angiography were performed and these studies did not show any abnormal findings. However, Tc-99m ECD brain SPECT showed diffuse hypoperfusion in the left cerebral hemisphere and blood cyclosporine level was 962.6 ng/ml. Cyclosporine administration was stopped and discontinuation of cyclosporine resulted in disappearance of all neurological symptoms. The same neurological symptoms recurred with cyclosporine re-administration for management of exacerbated graft versus host disease. In this case, Tc-99m ECD brain SPECT proved very helpful in the diagnosis of cycloporine neurotoxicity.
Angiography ; Brain ; Cerebrum ; Cyclosporine* ; Diagnosis ; Female ; Graft vs Host Disease ; Humans ; Lymphoma ; Magnetic Resonance Imaging ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Seizures ; Tomography, Emission-Computed, Single-Photon

Severe aplastic anemia (SAA) patients without an HLA-matched sibling donor need alternative treatment options. Umbilical cord blood transplantation (UCBT) has become an alternative means for treating various diseases, but it has not been proved to be a satisfactory method to treat SAA. Here, we report the case of a girl who underwent successful two-unit UCBT after engraftment failure with a single unit. Twounit UCBT is proposed to have better engraftment potential and to offer a better chance of survival, according to some reports. Increased cell dose and graft-versus-graft reaction could contribute to these advantages. With this promising result, two-unit UCBT could be an alternative treatment option for patients with SAA without an HLA-matched donor.
Anemia, Aplastic/diagnosis/*therapy ; Child, Preschool ; *Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease/immunology ; HLA Antigens/immunology ; Histocompatibility ; Humans ; In Situ Hybridization, Fluorescence

PURPOSE: Graft-Versus-Host Disease (GVHD) is a rare (0.1~2%) but severe complication after liver transplantation (LT). It is the most lethal complication after LT and there are currently no effective preventive or therapeutic measures available. Approximately 90 such cases have been reported in the literature, but only one case has been reported in Korea. METHODS: We performed a retrospective analysis of 767 patients who underwent LT (living donor:deceased donor=554:213) at Seoul National University Hospital, Korea from 1998 to 2009. Four patients (4/767, 0.52%) with histologically proven GVHD were found. The diagnosis of GVHD was made according to observing macrochimerism in the peripheral blood and the affected tissue biopsy. RESULTS: Four patients underwent LT due to Hepatitis B virus-related liver cirrhosis and two of these patients had coexisting hepatocellular carcinoma. Three patients received livers from deceased donors and one received a liver from a live donor. All their blood matching were identical. The first diagnosed case underwent human leukocyte antigen (HLA) typing only after LT and it showed complete one-way donor-recipient HLA matching. The onset of GVHD occurred between 10 days and 55 days after LT. All the patients developed high-grade fever, skin rash, neutropenia, diarrhea and the main signs and symptoms related to GVHD. All the patients died because of sepsis despite intensive treatment. CONCLUSION: GVHD after LT is an extremely rare and fatal complication and it is difficult to diagnose. Therefore, we should perform pre-transplant HLA matching and try to establish an early diagnosis for patients who are clinical suspicious of having GVHD. Further study in this area is needed and physicians need to be alert to detect this malady.
Carcinoma, Hepatocellular ; Chimerism ; Diarrhea ; Early Diagnosis ; Exanthema ; Fever ; Graft vs Host Disease ; Hepatitis B ; Humans ; Korea ; Leukocytes ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Neutropenia ; Retrospective Studies ; Sepsis ; Tissue Donors

PURPOSE: We investigated the effects of pretransplant-transfusion on engraftment, graft versus host disease (GVHD) and graft rejection after bone marrow transplantation (BMT) in children with severe aplastic anemia who had HLA-identical sibling donor. METHODS: We reviewed retrospectively the medical records of 47 children with severe aplastic anemia who received grafts from HLA-matched sibling donor using same conditioning regimen (procarbazine, antithymocyte globulin, and cyclophosphamide) from September 1986 to May 2001. GVHD prophylaxis consisted of cyclosporine and short-term methotrexate. Patients receiving multiple transfusion more than 40 transfused units in total before BMT were defined as high-risk group (HRG) and those with less than 40 transfused units were as standard-risk group (SRG). RESULTS: Among 47 patients, 30 patients were classified into SRG and remaining 17 were into HRG. The median time from diagnosis to transplant was 4 (range, 1~14) months in SRG and 36 (range, 3~360) months in HRG. Primary engraftment was achieved in all patients. Acute GVHD (> or =grade II) in HRG (13.3%) was comparable with in SRG (5.9%) (P=0.221), meanwhile corresponding fugures for chronic GVHD was 1 (3.3%) and 2 (11.8%). All of these patients have experienced complete resolution of GVHD and are no longer receiving immunosuppressive therapy. Booster stem cell infusion was needed for poor graft function (n=3) in SRG and also for poor graft function (n=1) or progressive rejection (n=3) in HRG. Five-year disease free survival rate was 100% in SRG and 94.1 6% in HRG (P=0.18). CONCLUSION: These findings suggest that multiple transfusion may be not a risk factor for rejection or poor outcome. Progressive rejection was observed only in patients with multiple transfusion but did not affect the survival.
Anemia, Aplastic* ; Antilymphocyte Serum ; Bone Marrow Transplantation* ; Bone Marrow* ; Child ; Cyclosporine ; Diagnosis ; Disease-Free Survival ; Graft Rejection ; Graft vs Host Disease ; Humans ; Medical Records ; Methotrexate ; Retrospective Studies ; Risk Factors ; Siblings* ; Stem Cells ; Tissue Donors* ; Transplants

Heavy proteinuria in the nephrotic range is an uncommon, often unrecognized manifestation of graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. A few isolated case reports have been published in the Korean literature involving a small number of patients who developed membranous nephropathy as GVHD after peripheral blood stem cell transplantation (PBSCT). A 17-year-old female was diagnosed with non-Hodgkin's lymphoma. Following remission, she underwent allogeneic PBSCT. Shortly thereafter, she developed acute GVHD, which was managed by medical therapy with prednisolone and cyclosporine. Approximately 13 months following PBSCT, the patient developed proteinuria without peripheral edema. Pulsed steroid therapy was initiated three times, but her condition did not improve. Twenty months after PBSCT, she developed nephrotic range proteinuria. A renal biopsy was performed, and the diagnosis was histologically consistent with membranous nephropathy. Because the response to steroids was not satisfactory, the dose of cyclosporine was increased. Approximately 3 months after renal biopsy, the proteinuria disappeared. Given the recent increase in the incidence of GVHD-mediated renal disease, in particular, renal biopsy is indispensable to the diagnosis of nephropathy and to the prevention of disease progression.
Adolescent ; Biopsy ; Cyclosporine ; Diagnosis ; Disease Progression ; Edema ; Female ; Glomerulonephritis, Membranous* ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Lymphoma, Non-Hodgkin ; Peripheral Blood Stem Cell Transplantation ; Prednisolone ; Proteinuria ; Stem Cells* ; Steroids

Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the disease. Chronic graft-versus host disease (GVHD) is a major complication of patients who have undergone allo-SCT. Nephrotic syndrome has been described as one of the rare manifestations of chronic GVHD following the usual myeloablative allo-SCT. We report a case of nephrotic syndrome that developed 25 months after non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient presented with preserved renal function and full nephrotic syndrome including generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive with a stable engraftment and full donor chimerism under the administration of tacrolimus for control of chronic GVHD and MG without refractory hemolysis and cytopenia.
Adult ; Diagnosis, Differential ; Female ; Glomerulonephritis, Membranous/drug therapy/*etiology/pathology ; Graft vs Host Disease/drug therapy/*etiology/pathology ; Hemoglobinuria, Paroxysmal/*therapy ; Human ; *Stem Cell Transplantation/*adverse effects ; Treatment Outcome