Hemophagocytic Lymphohistiocytosis in a Patient with Classical Hodgkin Lymphoma.

Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that can be associated with inherited genetic mutations, malignancy, autoimmune disorders, and viral infections. Though the pathogenesis is not fully known, HLH is understood to be a reactive process in the setting of uncontrolled activation of macrophages, CD8+ cytotoxic lymphocytes, and other immune cells. Hallmark clinicopathological features of HLH include fevers, cytopenias, hepatosplenomegaly, and hemophagocytosis in the bone marrow. Case Presentation. A previously healthy 28-year-old Caucasian male presented with a one-month history of persistent fever, night sweats, and unintentional weight loss. He was diagnosed with classical Hodgkin Lymphoma (HL) by core-needle biopsy of an axillary lymph node. Both bone marrow involvement by HL and hemophagocytosis were seen on subsequent bone marrow biopsy. Other findings included pancytopenia, splenomegaly, and elevated serum ferritin. Extensive work-up for autoimmune and infectious etiologies was unremarkable. The patient had a complete response after chemotherapy with Adriamycin, bleomycin, vincristine, and dacarbazine. Conclusion. This report documents the exceedingly uncommon association between HLH and HL. HLH is a hyperinflammatory syndrome with high mortality, so it is imperative to identify and treat the underlying cause for secondary HLH. Malignancy-associated HLH should be considered in the differential diagnosis for cancer patients who present with fever, cytopenias, and splenomegaly.

Allogeneic hematopoietic cell transplant for AML: no impact of pre-transplant extramedullary disease on outcome.

The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.

Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study.

The appropriate induction therapy before and the role of maintenance therapy after auto-SCT for patients with multiple myeloma remain areas of active investigation. We conducted a study in 40 patients with bortezomib given sequentially pre-auto-SCT and as maintenance therapy post auto-SCT. Pre-transplant bortezomib was administered for two cycles followed by high-dose melphalan 200 mg/m(2) with auto-SCT of G-CSF-mobilized PBMCs. Post transplant bortezomib was administered weekly for 5 out of 6 weeks for six cycles. No adverse effects were observed on stem cell mobilization or engraftment. An overall response rate of 83% with a CR+very good partial remission (VGPR) of 50% was observed with this approach. Three-year Kaplan-Meier estimates of disease-free survival and overall survival (OS) were 38.2 and 63.1%, respectively. Bortezomib reduced CD8(+) cytotoxic T cell and CD56(+) natural killer cell PBL subsets and was clinically associated with high rates of viral reactivation to varicella zoster.