Complete Regression Of Cutaneous B-cell Lymphoma In A Renal Transplant Patient After Conversion From Cyclosporin To Sirolimus
Mohsin, N., Budruddin, M., Kamble, P., Khalil, M., Pakkyarra, A., Jha, A., Mohammed, E., Ahmed, H., Ahmed, J., Thomas, S., Campistol, J. M., & Daar, A. (2007). Complete regression of cutaneous B-cell lymphoma in a renal transplant patient after conversion from cyclosporin to sirolimus. Transplantation proceedings, 39(4), 1267–1271. https://doi.org/10.1016/j.transproceed.2007.03.092
View Original Source →Abstract
Posttransplant lymphoproliferative disease remains a serious morbidity. Herein we have reported a case of complete regression of a biopsy-proven B-cell lymphoma that occurred in the posttransplant period. A 48-year-old man received a living donor renal transplant for end-stage renal disease due to undetermined etiology. His initial immunosuppression consisted of corticosteroid, mycophenolate mofetil, and cyclosporin. The patient developed severe pneumonia within the first 2 months after transplantation due to Acineotobacter, fungus, and cytomegalovirus infections. He experienced a complete recovery and was discharged for regional follow-up. Four months after discharge, he was referred again because of presence of two nodules on his trunk. A biopsy of the nodules revealed B-cell lymphoma. Cyclosporin was stopped and he was converted to sirolimus. The lesions regressed progressively and completely within 7 weeks. The patient remains well without clinical relapses at 19 months after conversion. Renal functions remained stable. We postulated that the antincoplastic properties of sirolimus may have played an active part in the positive outcome.
Case Details
Disease Location
Anterior chest wall and the back (skin)
Personal Characteristics
48 -year-old male renal transplant in june 2004, kidney failure cause was unknown but likely due to chronic glomerulonephritis
Clinical Characteristics
Patient didn't receive induction with antibodies, there was no transplant rejection, maintenance immunosuppression medication was prescribed. Was also receiving pneumocystis treatment. Cyclosporine c2 levles were around 1400 ng./ml serologies for hepatitis b, c and HIV were negative. Cytomegalovirus titer was initially positive for immunoglobulin IGG and negative for IGM. Serum creatinine at discharge was 110 micromol/l, liver enzymes were normal his condition was stable until 4 months later due to septicemia and severe respiratory infection with hypoxia requiring assisted ventilation in an icu. He also had a uti with coliforms, he was given antibiotics and cyclosporine and mycophenolate were stopped bronchoscopy found an inflamed left lung bronchus, bronchial lavage revealed fungal elements. Pneumocystis carinii and acid-fast bacilli were negative. Patient's condition worsened despite antifungal treatment. He developed leukopenia to 0.5x1.9; granulocyte colony stimulating factor was administered with good results and no rejection while serotology for cmv was negative, the cmv viral load by polymerase chain reaction was strongly positive with more than 14 million copies of DNA per milliliter IV gancyclovir was started for 21 days, renal function deteriorated and 3 dialysis sessions were needed. Renal function started to gradually improve and overall condition started to improve. After being discharged, the patient resumed cyclosporine and prednisolone. Mycophenolate was not resumed. 3 months later (march 2005) the patient was referred again for mildly reduced renal function and transplant hydroephrosis. Serum creatinine was 324 micromol/l. A nephrostomy was attempted but failed. Cystoscopy was performed and the bladder was incised. Renal function improved partially to reach a serum creatinine around 150micromol/l and then hovered around 170-190. Subsequent ultrasound of the transplant didnt now show hydroephrosis. Wbc count was low at 2.4x109 and the cmv pcr showed 12k copies/ml. He was administered IV gancyclovir for 14 days followed by oral valgancyclovir for 7 days. Wbc count returned to normal during that admission, clinical exam found two localized firm nodules over the anterior chest wall and the back. These nodules measured 4cm and 2.5 cm in diameter. Histopathological findings of an excisional biopsy were diffuse, nodular infiltrate with ulcerations. The infiltrate involved the dermis, the subcutis, appendage, and subcuticular fat. It was composed of monomorphus large cells with vesicular nuclei and prominent nucleoli that were CD20 and cd79a positive but CD10 negative ebv was focally positive, there were some cd45ro positive small lymphocytes in the background. Features were diagnostic of diffuse large ebv-associated lymphoma. The ebv pcr was not available, but one year later was positive with 2k copies/ml these lesions were localized to the skin, there were no signs of cerebral involvement. Bone marrow aspiration was normal, CT scan of chest and abdomen didnt show any masses or lymph nodes. Lactate dehydrogenase was normal. It was decided to switch from cyclosporine to sirolimus
Remission Characteristics
After dialysis the patient was discharged 4 weeks later with a serum creatinine of 133 micromol/l and a white cell count of 3.4x 109. After the second referral, after the administration of IV gancyclovir and oral valgancyclovir, wbc count returned to normal 3 weeks after switching to sirolimus, the lesions were noticeable smaller. Regression was completed at 7 weeks with no recurrence since 19 months after the switch, there was no rejection. Condition remains excellent and no significant morbidity. Renal function remains plateaued at around 190-210 micromol/l. Mycophenolate was reintroduced in april 2006 remains in complete remission for 2 years after switching with serum creatinine of 120-130 micromol/l
Treatment & Mechanisms
Proposed Remission Mechanisms
Conversion from cyclosporine, a calcineurin inhibitor, to sirolimus, an mtor inhibitor reduction of immunosuppressants
Clinical Treatment
Maintenance immunosuppression treatment was cyclosporin, mycophenolate mofetil, and prednisolone prophylaxis for pneumocystis with cotrimoxaole antibiotics for uti antifungal treatment with liposomal amphotericin b granulocyte colony stimulating factor IV gancyclovir was started and continued for 21 days 3 dialysis sessions were needed for deteriorated renal function after being discharged, the patient resumed cyclosporine and prednisolone. Mycophenolate was not resumed. He was administered IV gancyclovir for 14 days followed by oral valgancyclovir for 7 days excisional biopsy cyclosporine was replace with sirolimus mycophenolate was eventually reintroduced
Non-Clinical Treatment
None reported