Amar, Surabhi

Post-transplant lymphoproliferative disorders (PTLD) are B-cell disorders characterized by abnormal lymphoid proliferation due to immunesuppression mediated T-cell dysfunction after organ transplantation, and carry a poor prognosis. Reduction of immunesuppression is the first line of therapy but involves the risk of allograft rejection. Anti-viral agents like acyclovir, intravenous immunoglobulin, interferon-α, anti interleukin -6 antibodies, chemotherapy and rituximab are other treatments that have been tried with limited success. EBV-specific adaptive immunetherapy is promising but only available in a few centers. Prognosis is poorer in patients with relapsed disease. We report the case of a 46 year-old liver transplant recipient, with recurrent PTLD after liver transplantation, who was successfully treated with high dose chemotherapy followed by autologous bone marrow transplant (ABMT). He had undergone an orthotopic liver transplant (OLT) 13 years ago for primary sclerosing cholangitis. PTLD (EBV related, Hodgkin like, CD20+ and CD30+) developed 7 years ago, and initially resolved with ganciclovir and reduction of immunesuppression. The patient relapsed 5 years later. Immunesuppression was discontinued and 3 cycles of rituximab with CHOP (R-CHOP) followed by 4 doses of R at weekly intervals were given leading to complete response. Four months later, he again relapsed and responded to 4 more cycles of R-CHOP. He was referred to our center for transplant evaluation. Progenitor cell mobilization with filgrastim was unsuccessful. He underwent an unstimulated bone marrow harvest yielding 1.02 × 10 6 CD34 cells/kg. Transplant conditioning was with R-BEAM. Because of abnormal liver function tests and concern for further hepatotoxicity, carmustine dose was reduced by 50%. Immunesuppression for OLT was withheld during the transplant period. He tolerated the chemotherapy well but had delayed neutrophil and platelet engrafment (days +31 and +50 respectively). Liver functions deteriorated in the post transplant period, but responded to reinitiation of prednisone and tacrolimus on days +41 and +50, respectively. Post transplant PET/CT imaging performed on day+45 revealed complete resolution of his lymphadenopathy. He continues to be asymptomatic with no evidence of relapse days+ 72 after transplant, at the time of this writing. ABMT is the standard of care for chemotherapy-sensitive relapsed lymphomas. However, the complexity of ABMT after a prior solid organ transplant limits its use for relapsed PTLD. There is a higher likelihood of regimen-related toxicity, and immunesuppression needs to be carefully managed. While it is desirable to reduce immunesuppression during the transplant period to minimize infections and to control PTLD, this has to be balanced against the risk of solid organ graft rejection. This is particularly critical in patients with liver transplantation in whom (unlike renal graft) loss of liver graft may be fatal. There are only 6 previous cases of PTLD treated with stem cell transplant, but none of these patients had a prior OLT. Our experience with this case suggests that autologous bone marrow transplant can be a potential treatment option for patients with recurrent PTLD in selected patients. Appropriate dose modification of conditioning regimen and careful management of peritransplant immunesuppression appears important for successful outcome.

Abstract Long-term outcomes and hence the role of adjuvant therapy in patients with small (≤1 cm), node-negative breast cancer remain unclear. This study's objective was to evaluate whether human epidermal growth factor receptor (HER)-2 status is an independent, poor prognostic marker in patients with these tumors and to identify a subgroup of patients with these small tumors who might benefit from adjuvant systemic therapy. All patients with a diagnosis of a node-negative breast tumor measuring ≤1 cm and available HER-2 test results between January 1, 2001, and December 31, 2005, at the three Mayo Clinic sites were identified. Clinicopathologic data were compared in three groups: HER-2−, HER-2+, and triple-negative (TN) tumors. Of the 421 tumors identified, 364 (86.5%) were HER-2−, 28 (6.7%) were HER-2+, and 29 (6.9%) were TN. The median follow-up time was 1,015 days (range, 1–2,549 days). Groups were balanced in terms of patient age and tumor histology. Eleven patients with HER-2− tumors (3.0%), seven with HER-2+ tumors (25.0%), and eight with TN tumors (27.6%) received adjuvant chemotherapy. Follow-up data were available for 357, 28, and 28 patients in the three groups, respectively. Death rates in the three groups were 6.4% (23 of 357) (one recurrence-related death), 0% (0 of 28), and 7.1% (2 of 28) (one recurrence-related death), respectively. During follow-up, the tumor recurred in nine patients: four were HER-2− tumors (1.1%), two were HER-2+ tumors (7.1%), and three were TN tumors (10.7%). Patients with small, node-negative breast tumors have an excellent prognosis, but HER-2+ and TN tumors appear to have a higher recurrence rate, warranting consideration for broad use and optimization of systemic adjuvant treatments.