Zachariah DeFilipp

Secondary solid cancer screening following hematopoietic cell transplantation.

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31–49% amongst HCT recipients. While MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Intravenous iron replacement for persistent iron deficiency anemia after Roux-en-Y gastric bypass

BACKGROUND Iron deficiency is a major postoperative complication of Roux-en-Y gastric bypass surgery. Oral replacement can fail to correct the deficiency. Thus, recourse to parenteral iron administration might be necessary. Our objective was to evaluate the effectiveness and safety of a standardized 2 g intravenous iron dextran infusion in the treatment of iron deficiency after Roux-en-Y gastric bypass surgery. The setting was a university-affiliated community hospital in the United States. METHODS We reviewed the medical records of 23 patients at our institution who had received 2 g of iron dextran intravenously for recalcitrant iron deficiency after Roux-en-Y gastric bypass surgery. We obtained the demographic data and the complete blood count and serum iron studies obtained before treatment and at outpatient visits after infusion. RESULTS Before treatment, all 23 patients were iron deficient (average ferritin 6 ng/mL) and anemic (average hemoglobin 9.4 g/dL). By 3 months, the average ferritin and hemoglobin had increased to 269 ng/mL and 12.3 g/dL, respectively. The hemoglobin levels remained stable throughout the follow-up period. The iron stores were adequately replaced in most patients. Four patients required a repeat infusion by 1 year, because the ferritin levels had decreased to <15 ng/mL. The probability of remaining in an iron replete state was 84.6% (95% confidence interval 78-91.2%). One patient required warm compresses for superficial phlebitis. No other significant adverse events were reported. CONCLUSION Intravenous administration of 2 g of iron dextran corrects the anemia and repletes the iron stores for ≥1 year in most patients. This therapy is safe, tolerable, efficient, and effective.

High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission: ASCT for Primary CNS Lymphoma in CR1

High‐dose chemotherapy and autologous stem cell transplantation (HDC‐ASCT) is a therapeutic option for patients with primary central nervous system lymphoma (PCNSL). To the authors’ knowledge, data are limited regarding its use among patients in first complete remission (CR1) with the CNS‐directed conditioning regimen of thiotepa, busulfan, and cyclophosphamide (TBC).

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31–49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity

We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.

Long-term outcomes among 2-year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b-cell lymphoma: Long-Term Outcomes After Auto-HCT

Autologous hematopoietic cell transplantation (auto‐HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL); however, long‐term outcomes are not well described.

Cytogenetic risk determines outcomes after allogeneic transplantation in older patients with acute myeloid leukemia in their second complete remission: A Center for International Blood and Marrow Transplant Research cohort analysis

Allogeneic hematopoietic cell transplantation (HCT) offers curative potential to a number of older patients with acute myeloid leukemia (AML) in their first complete remission. However, there are limited data in the literature concerning post‐HCT outcomes for older patients in their second complete remission (CR2).

Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.

Management of Advanced-Phase Chronic Myeloid Leukemia

The management of chronic myeloid leukemia (CML) in accelerated or blast phase (advanced phase) remains a significant challenge despite the introduction of very effective tyrosine kinase inhibitors (TKIs). The biology of advanced-phase CML is complex and engages several pathways that are not optimally targeted by TKIs. Allogeneic stem cell transplantation remains the only potentially curative therapy, but the effectiveness of this conventional approach is limited. New strategies are required to improve the outlook for these patients.