Temsirolimus as base immunosuppressant for a recipient with metastatic renal cancer: adequate immunosuppression and oncological control--case report.

Treating organ recipients who have metastatic renal cell carcinoma (mRCC) is challenging because of the dilemma between transplant-required immunosuppression and cancer control via boosting immunity with immunotherapy. We report such a patient whose case was successfully maintained only with temsirolimus and low-dose steroids, while achieving good allograft function and oncological outcomes. After removal of his primary renal cancer, a kidney recipient was found to have multiple metastases. Since recovery from surgery he has been administered 25 mg/wk temsirolimus for 2 more years. His mRCC is in partial remission, the serum creatinine level has been stable (∼ 1.6 mg/dL), and the performance score has been good. Adverse effects encountered include transient transaminitis, dyslipidemia, and poorly controlled hyperglycemia. The pharmacokinetics of sirolimus (the major first metabolite of temsirolimus) is depicted to speculate the underlying mechanism. To our knowledge, this is the first sustainable success using temsirolimus-based immunotherapy (both immunosuppression and cancer therapy) in a transplant recipient who has mRCC.

Lymphocyte subsets associated with T cell receptor beta-chain gene rearrangement in patients with rheumatoid arthritis and neutropenia.

OBJECTIVE: To determine the incidence of a clonal lymphoid disease in patients with chronic rheumatoid arthritis (RA) and neutropenia. METHODS: Lymphocytes from 23 RA patients with either current neutropenia or a history of this complication were studied. RESULTS: Eight patients had a clonal rearrangement of the T cell receptor beta-chain gene. Phenotypically, they showed a distinctive pattern characterized by an inverted CD4+:CD8+ cell ratio and an increased number and percentage of CD57+/CD8+ and CD3+/DR+ lymphocytes. None had evidence of a lymphoid malignancy. CONCLUSION: Among RA patients with neutropenia, there is a subset who have a subclinical disease resembling T gamma lymphoproliferative disease.

Eosinophilia resulting from administration of recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in a patient with T-gamma lymphoproliferative disease.

A therapeutic trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was attempted in a patient with neutropenia and frequent infections secondary to T-gamma lymphoproliferative disease (T-gamma LPD). During the 14 days of subcutaneous rhGM-CSF (500 micrograms/m2/day), the absolute eosinophil count increased from 0 to 9,455/microliters. By contrast, the absolute neutrophil count decreased. Toxicity related to rhGM-CSF included arthralgia and nonspecific chest pain. The possible mechanism for the rhGM-CSF induced selective eosinophilia is discussed.

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow for acute lymphoblastic leukemia.

Ten patients age 13-52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily x 4 and total body irradiation 3 Gy daily x 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100-120 micrograms/ml. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 +/- 0.7 x 10(8)/kg, and the CFU-GM content of the transplant was 0.4 +/- 0.5 x 10(3)/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 x 10(9)/L at a median of 26 days and platelets exceeded 50 x 10(9)/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2-9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43+, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.

Acute tumor lysis syndrome in a patient with chronic myelogenous leukemia in blast crisis: role of high-dose Ara-C.

A patient with chronic myelogenous leukemia (CML) in lymphoid blast crisis developed acute tumor lysis syndrome following administration of high-dose busulfan, cyclophosphamide and cytarabine (Ara-C) in preparation for allogeneic bone marrow transplantation. Preconditioning cytoreduction, close monitoring and rapid institution of therapeutic measures were required to avoid renal failure and a fatal outcome. Acute tumor lysis syndrome has not been reported in marrow transplant patients receiving conventional preparative regimens as treatment for CML in blast crisis, and it is likely that its occurrence in this patient was precipitated by high-dose Ara-C.

Chimerism studies using in situ hybridization for the Y chromosome after T cell-depleted bone marrow transplantation.

In situ hybridization for the Y chromosome (Y-ISH) was used to monitor engraftment in 10 patients with hematological malignancies who had received T cell-depleted marrow transplants from sex-mismatched donors, seven of whom were only partially HLA-matched. In the three patients who engrafted, as the peripheral counts rose, the percentage of host peripheral blood and marrow mononuclear cells decreased steadily, although host cells (less than 1%) could still be detected as late as day 252. The percentage of host granulocytes fell rapidly to less than 0.2%. Seven patients did not achieve full engraftment by day 28. Those with a low percentage of host cells (less than 1%) improved with observation or treatment with steroids, while those with a high or increasing percentage of host cells did not improve even after treatment with GM-CSF or with repeat marrow infusion without reconditioning. In one patient with graft failure, the residual host cells were predominantly CD8+ CD57+ and CD3+ CD56+, phenotypes consistent with non-MHC-restricted cytotoxic T cells. Lack of full engraftment in recipients of T cell-depleted marrow is not always associated with autologous reconstitution and does not always require retransplantation. Y-ISH may be useful for monitoring patients at high risk for graft failure in order to detect adverse trends in mixed chimerism that will alter therapy early after transplantation.