Successful Allogeneic Stem-Cell Transplantation in a Patient With Myelodysplastic Syndrome With Hemodialysis-Dependent End-Stage Renal Disease (2011)

Despite the use of a reduced-intensity conditioning regimen for recipients of allogeneic stem-cell transplantation (allo-SCT) with renal impairment, patients with end-stage renal disease (ESRD) who require dialysis have been excluded from allo-SCT because of high risk of transplant-related death. Therefore, only a few cases of allo-SCT in patients with nonmalignant hematologic disease who are on dialysis have been reported (1–4), and no case of successful allo-SCT in malignant patients on dialysis has been reported, even in patients with myeloma-associated ESRD. The reason is that the risk of transplant-related mortality in allo-SCT is expected to be much higher for malignant hematologic disease, compared with nonmalignant disease, even in patients with normal renal function. A 61-year-old man with ESRD caused by diabetic nephropathy was referred to the hematology department with pancytopenia requiring regular transfusional support every 2 weeks. He had been on hemodialysis (HD) for 5 years. Bone marrow examination revealed 7% blasts and three-lineage dysplasia, which led to a diagnosis of refractory anemia with excess blasts-1. The karyotype of bone marrow cells was 46XY. Based on the World Health Organization–adapted prognostic scoring system of myelodysplastic syndrome, he was in a high-risk group. The patient received six cycles of decitabine treatment; however, there was no response. He underwent allo-SCT from a mismatched (one allele and one antigen-mismatched) unrelated donor. The conditioning regimens were fludarabine (15 mg/m2/day for 5 days), melphalan (50 mg/m2/day for 2 days), and total body irradiation (400 cGy). Antithymocyte globulin (1.25 mg/kg/day for 2 days) was given before transplantation for prophylaxis of acute graft-versus-host disease (GvHD). Doses of fludarabine and melphalan were adjusted based on previous experimental reports (5–7). During the conditioning period, daily HD was performed for volume control. The stem-cell source was granulocyte colony stimulating factor-mobilized peripheral blood stem cells. The amount of infused CD34-positive cells was 8.99×1054/kg and that of CD3-positive cells was 37×1054/kg. Tacrolimus and mycophenolate mofetil were used for GvHD prophylaxis. For prevention of infection, acyclovir, micafungin, and sulfamethoxazole/trimethoprim were prescribed. The engraftment was successful. Neutrophil and platelet count showed recovery at day 12 posttransplant, and donor chimerism measured using polymerase chain reaction (PCR) analysis of short tandem repeat sequences in bone marrow cells at day 22 posttransplant revealed 100% of donor type. However, the posttransplant clinical course was complicated. On the 12th day posttransplant, sinusoidal obstruction syndrome developed and total bilirubin level was increased up to 8.1 mg/dL. Mycophenolate mofetil was discontinued, and recombinant tissue plasminogen activator was administered. The sinusoidal obstruction syndrome was resolved with a 4-day treatment of recombinant tissue plasminogen activator. From day 15 posttransplant, grade III gut GvHD developed; however, it was resolved with methyl prednisolone treatment. After discharge, he was admitted to the hospital three times because of recurrent diarrhea. The gut GvHD was steroid-respondent but dependent at the first two admissions; however, it became steroid-resistant at the third admission. Only after treatment with antithymocyte globulin, the steroid-resistant GvHD was resolved. Two weeks after resolution of diarrhea, fever and pancytopenia developed. Bone marrow biopsy revealed active hemophagocytosis, and quantitative PCR for Epstein-Barr virus (EBV) indicated a high load of EBV DNA in bone marrow cells. PCR for short tandem repeat was 100% of donor type in bone marrow cells.Immunosuppressant was tapered off for EBV-associated hemophagocytosis, and the complete blood count showed a slow recovery. He is still alive and disease free without transfusional support, maintaining full donor chimerism. This is the first reported case of successful allo-SCT of a dialysis patient with malignant hematologic disease. Over- or underdosing of conditioning regimens may result in the death of those patients owing to unacceptable regimen-related toxicity or engraftment failure. This case indicates that dose-adjusted fludarabine, melphalan, and total body irradiation are sufficient and tolerable preparative regimens for allo-SCT in patients with hematologic malignant disease with ESRD requiring HD. All drugs used in treatment of the patient should be dialyzable or both metabolized and excreted by organs other than kidney because serum level of those drugs can be lowered with dialysis or spontaneously in the case of drug toxicity. Another considerable risk in posttransplant patients on HD is the high risk of infection. Because the immunity of HD patients is depressed, compared with normal individuals (8, 9), posttransplant infection risk for HD patients can be higher than that of patients with normal renal function. Because the risk of posttransplant complications may be high and treatment of these patients is extremely difficult, as described above, allo-SCT for those patients should be performed only in a highly experienced transplantation center. Hong Seok Choi1 Sung-Yong Kim1 Jong-Ho Lee2 So Young Yoon1 Yo-Han Cho1 Hong Ghi Lee1 1Department of Hemato-oncology KonKuk University Medical Center KonKuk University, Seoul, Korea 2Department of Nephrology KonKuk University Medical Center KonKuk University, Seoul, Korea