Sigal Grisariu

Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report.

Neurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%. It occurred as the initial manifestation of malignancy in 26% of cases. The affected neural structures included peripheral nerves (60%), spinal nerve roots (48%), cranial nerves (46%), and plexus (40%) with multiple site involvement in 58%. Imaging studies often suggested the diagnosis with 77% positive magnetic resonance imaging, and 84% (16 of 19) positive computed tomography-positron emission tomography studies. Cerebrospinal fluid cytology was positive in 40%, and nerve biopsy confirmed the diagnosis in 23 of 26 (88%). Treatment in 47 patients included systemic chemotherapy (70%), intra-cerebrospinal fluid chemotherapy (49%), and radiotherapy (34%). Response to treatment was observed in 46%. The median overall survival was 10 months, with 12- and 36-month survival proportions of 46% and 24%, respectively. NL is a challenging diagnosis, but contemporary imaging techniques frequently detect the relevant neural invasion. An aggressive multimodality therapy can prevent neurologic deterioration and is associated with a prolonged survival in a subset of patients.

The humoral immune response of hematopoietic stem cell transplantation recipients to AS03-adjuvanted A/California/7/2009 (H1N1)v-like virus vaccine during the 2009 pandemic.

We evaluated the formation of hemagglutination-inhibition (HI) antibodies in response to vaccination of 55 allogeneic and 23 autologous hematopoietic stem cell transplantation (HSCT) recipients with 3.75 μg inactivated influenza A/California/7/2009 (H1N1)v-like virus adjuvanted with AS03, given towards the end of the 2009 influenza pandemic. The 78 HSCT recipients, aged 11-72 (median 50) years, were vaccinated 1-290 (median 27) months post-HSCT. Of the 55 allogeneic HSCT recipients, 50.9% received reduced intensity conditioning, 74.5% had a sibling donor, 67.2% had active graft-versus-host disease and 43.6% were on steroid therapy. At baseline, 14/78 (17.9%) had HI titers ≥ 1:40. Blood samples of 77 patients were available post-1st vaccination; of these, 34 (44.2%) patients had HI titers ≥ 1:40. Blood samples of 43 patients were available post-2nd vaccination; of these, 21 (48.8%) had HI titers ≥ 1:40. There was a significant increase in HI titers ≥ 1:40 from baseline to both post-1st and 2nd vaccinations (p<0.001 each), and also from 1st to 2nd vaccination (p=0.008). In seronegative (HI titers <1:10) patients, whose sera were available before, after one dose, and after 2 doses of vaccine, seroconversion (to ≥ 1:40) occurred in 4/24 (16.7%) after 1-dose and in a total of 10/24 (41.7%) after 2-dose vaccination (p=0.031). Logistic regression analysis revealed that ≥ 1:40 HI titers were significantly associated with higher lymphocyte counts and higher HI baseline titers and, in allogeneic HSCT, with having a sibling donor and higher baseline titers. In conclusion, 2-dose vaccination with AS03-adjuvanted vaccine containing 3.75 μg antigen resulted in a statistically significant, yet limited, serological response. Therefore, additional precautions should be taken during influenza outbreaks.

Clinical implications of acute myeloid leukemia presenting as myeloid sarcoma.

In this retrospective study, we aim to analyze the characteristics, treatments, and overall survival of all patients presenting with isolated myeloid sarcoma (MS) or MS with concomitant acute myeloid leukemia (AML) compared with all patients with AML, treated during the same period. We identified patients with AML with or without MS at diagnosis, presenting to our medical center between the years 1990 and 2005. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission, number of cycles of chemotherapy needed to achieve complete remission, and rate of first relapse. The time to death in the MS group was not significantly different (p = 0.60) from the AML group, and radiotherapy did not affect the median time to death. Transplantation prolonged survival in both groups (p = 0.018 and p < 0.0001, respectively). Patients with MS at diagnosis might benefit from upfront aggressive treatment with hematopoietic stem cell transplantation. Copyright

Bleeding, Obstruction, and Perforation in a Series of Patients With Aggressive Gastric Lymphoma Treated With Primary Chemotherapy

BackgroundThe management of patients with gastric lymphoma has evolved, with a shift toward nonsurgical treatment. The rates of surgical complications in patients receiving chemotherapy have been insufficiently studied. The objective of this study was to assess the frequency of bleeding, perforation, and gastric outlet obstruction in patients who received chemotherapy as primary treatment for gastric diffuse large B cell lymphoma (DLBCL).MethodsWe reviewed files of all patients with gastric DLBCL who were diagnosed and treated primarily with chemotherapy in our hospital between 1990 and 2005.ResultsEighteen (25%) of 73 patients experienced surgical complications, of whom 6 (8%) underwent surgery. Eight patients (11%), six with active lymphoma, experienced gastric bleeding; one required gastrectomy. Eight patients (11%) developed gastric outlet obstruction, of whom three were treated conservatively, three required surgery, one stopped treatment, and one received further chemotherapy. Six of the eight patients had no evidence of active lymphoma at the time of obstruction. Two additional patients underwent gastrectomy due to resistant or relapsed disease. Gastric perforation was not observed. Median survival was 90 months for the entire series, 94 months for patients with gastric outlet obstruction, and 11.5 months for patients with gastric bleeding.ConclusionsGiven the rate of surgical complications, especially gastric bleeding and gastric outlet obstruction, there is still an important role for the surgical consultant in the treatment of patients with gastric DLBCL receiving chemotherapy. Gastric perforation, although frequently cited as a complication, is in fact rarely observed.

Enteroviral infection in patients treated with rituximab for non-Hodgkin lymphoma: a case series and review of the literature

In recent years, anti‐CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life‐threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B‐cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis

Daratumumab is a promising new antimyeloma agent. We report a single center “real‐world” series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab.

The effect of cyclosporine initiation time on the outcome of matched allogeneic stem-cell transplantation following fludarabine-based conditioning

Cyclosporine (CSA) is the most commonly used medication for GVHD prophylaxis. The initiation time varies from day −4 to day 0. Initially, we gave CSA starting on day −1. However, since 2003 we have changed CSA initiation timing policy in most of our protocols to day −4, to achieve stable and controlled pretransplant CSA levels. Here, we assessed if initiation time impact the outcome of allogeneic stem‐cell transplantation (allo‐SCT). Data of 261 patients who underwent allo‐SCT for hematological malignancies from a fully matched donor, treated with CSA as a single agent for GVHD prophylaxis were prospectively collected. Patients were divided according to CSA initiation time and analyzed for outcome. The acute GVHD severity, cGVHD extent, GVHD‐associated mortality were significantly lower in the CSA −4 group. There was no difference in the rate and timing of acute or chronic GVHD. Overall survival did not differ between the groups. We conclude that the initiation of CSA at day −4 reduced the severity of aGVHD, extent of cGVHD, and GVHD‐associated mortality without impact on overall survival.

Thiotepa, Etoposide, Cyclophosphamide, Cytarabine, and Melphalan (TECAM) Conditioning Regimen for Autologous Stem Cell Transplantation in Lymphoma

Background High‐dose chemotherapy and autologous stem cell transplantation (ASCT) is the current standard of care for relapsed non‐Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Conditioning regimens with high‐dose carmustine have been associated with idiopathic pneumonitis syndrome. We, therefore, created a modified alternative TECAM conditioning regimen, consisting of etoposide, thiotepa, cytarabine, cyclophosphamide, and melphalan. Patients and Methods We retrospectively analyzed our cohort of 212 NHL and HL patients, who had undergone ASCT with the TECAM conditioning regimen from 2000 to 2013. Although toxicity and engraftment were analyzed for all 212 patients, the survival analysis was performed for the 2 largest groups of patients, those with diffuse large B‐cell lymphoma (DLBCL) and those with HL (n = 127) to minimize heterogeneity. Results The 3‐year overall survival among the DLBCL and HL patients was 0.618 (95% confidence interval [CI], 0.490‐0.722) and 0.828 (95% CI, 0.701‐0.904), respectively. Stage IV disease at transplantation was a statistically significant poor prognostic factor. Higher Eastern Cooperative Oncology Group performance status and progressive disease at transplantation were found to be borderline significant. No idiopathic pneumonitis syndrome cases were reported in our cohort. Six patients died of treatment‐related toxicity during the first 100 days. The 3‐year progression‐free survival was 0.5 (95% CI, 0.37‐0.61) for HL patients and 0.49 (95% CI, 0.36‐0.60) for DLBCL patients. Conclusion Our results are encouraging and justify evaluation of TECAM versus BEAM (carmustine, etoposide, cytarabine, melphalan) in a prospective multicenter study in a large homogenous patient population. Micro‐Abstract High‐dose chemotherapy and autologous stem cell transplantation (ASCT) is the current standard of care for relapsed lymphoma. We retrospectively analyzed the data from 212 lymphoma patients who had undergone ASCT with the TECAM conditioning regimen. The 3‐year overall survival, progression‐free survival, and death resulting from treatment were comparable to those reported with other conditioning regimens. Our results justify evaluation of TECAM in a prospective multicenter study.

Fludarabine-based reduced toxicity yet myeloablative conditioning is effective and safe particularly in patients with high-risk thalassemia undergoing allogeneic transplantation

Thalassemia major (TM) is an inherited disorder caused by ineffective erythropoiesis. At the present time, allogeneic stem cell transplantation (allo‐SCT) is a curative option. Conventional busulfan and cyclophosphamide based myeloablative conditioning regimens are limited by increased toxicity, especially in high‐risk patients. Replacement of cyclophosphamide with fludarabine has reduced toxicity and nonrelapse mortality (NRM), thus improving outcomes. We analyzed long‐term data of our fludarabine‐based myeloablative, reduced toxicity protocol, specifically in high‐risk patients.

Successful hematopoietic stem cell transplantation for osteopetrosis using reduced intensity conditioning

Infantile malignant osteopetrosis (IMO) is an autosomal recessive condition characterized by defective osteoclast activity, with hematopoietic bone marrow transplant being the only available cure. Over the past several years, new conditioning regimes and donor options have emerged, thus extending the possibility of cure to a greater number of patients and improving the outcomes of bone marrow transplant. Here we detail the outcomes of bone marrow transplant in a cohort of 31 patients treated with a combination of fludarabine, treosulphan, thiotepa, and antithymocyte globulin.