The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.

The development of sensitive and non-invasive "liquid biopsies" presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era.

OBJECTIVES AND METHODS: Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. RESULTS: Over a median follow-up of 37.8 (range 6-167.1) months, Kaplan-Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin <12 g/dl was associated with inferior OS (p = 0.045). High-risk FLIPI score was associated with inferior PFS when compared with intermediate/low risk (p = 0.05) and marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. CONCLUSION: Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience

ABSTRACT Introduction: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. Methods: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. Results: Forty-one patients were reviewed: 10 (24%) had Hodgkin's and 31 (76%) had non-Hodgkin lymphomas. The median age was 50 years and 23 (56%) were male. The majority of patients (68%) had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43%) patients were in complete and seven (17%) were in partial remission. Most (95%) patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. Conclusions: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. METHODS: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. RESULTS: Forty-one patients were reviewed: 10 (24%) had Hodgkin's and 31 (76%) had non-Hodgkin lymphomas. The median age was 50 years and 23 (56%) were male. The majority of patients (68%) had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43%) patients were in complete and seven (17%) were in partial remission. Most (95%) patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. CONCLUSIONS: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

Dual institution experience of nodal marginal zone lymphoma reveals excellent long-term outcomes in the rituximab era.

Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin lymphoma that arises from mature B-cells. We delineate outcomes, prognostic factors and treatment trends among a large cohort of patients with NMZL in the rituximab era. We identified 56 such patients treated at our institutions. The majority presented with advanced stage disease (78·6%). Over a median follow-up of 38·2 months, median progression-free survival (PFS) was 42·4 months and median overall survival (OS) was not reached. Kaplan-Meier estimates of OS at 120 months after diagnosis was 71·9%. High-risk follicular lymphoma international prognostic index (FLIPI) was associated with inferior PFS. Age >60 years and elevated serum lactate dehydrogenase (LDH) were associated with inferior OS. Transformation to diffuse large B-cell lymphoma occurred in 7 patients, 6 of who presented with advanced disease. OS was comparable to our previously reported extranodal MZL cohort. FLIPI score predicted for inferior PFS and OS when both cohorts were analysed together (n = 267). In summary, outcomes in NMZL are favourable with a large majority of patients surviving at 120 months. High risk FLIPI, age >60 years, and elevated serum LDH were associated with inferior outcomes.

Dual institution experience of extranodal marginal zone lymphoma reveals excellent long-term outcomes.

Extranodal marginal zone lymphoma (EMZL) is a B-cell lymphoma arising from mucosa-associated lymphoid tissue (MALT). The disease characteristics, clinical course and treatment vary considerably based on site of involvement. Because long-term outcome data for EMZL are limited, we sought to describe the clinical details of a large number of patients with EMZL evaluated at the Case Comprehensive Cancer Center over a 12-year period to identify prognostic markers including the impact of site of involvement. We identified 211 cases of EMZL involving the stomach (30%), ocular adnexa (19%), lungs (16%) and intestines (9%). Initial treatment included antibiotics (18%), radiation (21%), rituximab (20%), chemotherapy (3%), rituximab + chemotherapy (7%), surgery (17%) or observation (8%). After a median follow-up of 44·3 months (range 2·2-214·9), median progression-free survival (PFS) was 68·2 months (95% confidence interval [CI] 54·5-111·3) and median overall survival (OS) has not been reached. Age >60 years, elevated lactate dehydrogenase level (LDH), ≥4 lymph node groups involvement, and high follicular lymphoma international prognostic index (FLIPI) were associated with inferior PFS/OS. In summary, patients with EMZL have excellent prognosis with median OS in excess of 10 years. Age, elevated LDH, advanced disease, and high FLIPI score are associated with worse outcomes.

Transmission of lupus anticoagulant by allogeneic stem cell transplantation.

Passive transmission of autoimmune diseases by allogeneic stem cell transplantation is rare and is ascribed to passive transfer of memory B-cells from donor to recipient. We hereby report a case of transmission of an asymptomatic lupus anticoagulant from a sibling donor to a recipient of transplantation for secondary acute myeloid leukemia. On pre-harvest evaluation, the sibling donor with no history of bleeding or thrombosis was found to have a lupus anticoagulant. After engraftment, the recipient was found to have a new prolonged activated partial thromboplastin time and was subsequently shown to have a lupus anticoagulant on Day +73 after stem cell transplantation. The recipient remained well with no evidence of bleeding, thrombosis, or graft-versus-host disease and was on a stable dose of tacrolimus at the time the lupus anticoagulant was detected. There was no other identifiable trigger for the appearance of a lupus anticoagulant.

Transmission of lupus anticoagulant by allogeneic stem cell transplantation

Passive transmission of autoimmune diseases by allogeneic stem cell transplantation is rare and is ascribed to passive transfer of memory B-cells from donor to recipient. We hereby report a case of transmission of an asymptomatic lupus anticoagulant from a sibling donor to a recipient of transplantation for secondary acute myeloid leukemia. On pre-harvest evaluation, the sibling donor with no history of bleeding or thrombosis was found to have a lupus anticoagulant. After engraftment, the recipient was found to have a new prolonged activated partial thromboplastin time and was subsequently shown to have a lupus anticoagulant on Day +73 after stem cell transplantation. The recipient remained well with no evidence of bleeding, thrombosis, or graft-versus-host disease and was on a stable dose of tacrolimus at the time the lupus anticoagulant was detected. There was no other identifiable trigger for the appearance of a lupus anticoagulant...