Adrienne Phillips

Cancer Incidence and Mortality in the Caribbean

Background: Nearly 10% of immigrants to the United States come from the Caribbean region. In this paper, we analyzed incidence and mortality rates of the major cancers in the Bahamas, Barbados, Cuba, the Dominican Republic, Haiti, Jamaica, Puerto Rico, and Trinidad and Tobago, and compared them with US patterns. Methods: We obtained age-standardized, sex-specific cancer incidence and mortality rates for cancers of the bladder, breast, cervix, esophagus, large bowel, liver, lung, pancreas, prostate, and stomach for 8 Caribbean countries and the United States from the GLOBOCAN program of the International Agency for Research in Cancer (IARC) and for the U.S. population from the Surveillance, Epidemiology, and End Results (SEER) Program of the NCI. Results: GLOBOCAN incidence and mortality rates for the overall United States were lower than but correlated with overall SEER rates. Based on GLOBOCAN data, the incidence and mortality rates of cancers of the breast, prostate, large bowel, and lung, and, among males, bladder cancer were lower in the Caribbean countries than the United States. Caribbean countries had higher rates of cancers of the cervix, esophagus, liver, and stomach. Haiti had the highest incidence and mortality rates of cervix and liver cancers. Jamaica and Haiti had the highest rates of stomach cancer. Conclusions: Cancer incidence and mortality in the Caribbean generally follow known patterns of association with economic development, infectious agents, and racial/ethnic origin. Studying these patterns and how immigration changes them may yield clues to cancer etiology. A better understanding of cancer incidence and mortality rates may help health policymakers to implement state-of-the-art treatment and preventive services for people of Caribbean descent both in their native countries and in immigrant communities in the United States.

Incidence and survival patterns of cutaneous T-cell lymphomas in the United States

Abstract Using the United States Surveillance, Epidemiology and End Results (SEER) 17 dataset, we examined incidence and survival patterns for patients with cutaneous T-cell lymphomas (CTCLs) diagnosed following institution of the World Health Organization–European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification. From 2005 to 2008, 2273 cases of CTCL were diagnosed. The age-adjusted incidence rate per 100 000 person-years for mycosis fungoides (MF) was 0.55 and for Sézary syndrome (SS) was 0.01. Incidence was higher among males (MF/SS male-to-female incidence rate ratio [IRR] 1.57) and black patients (MF black-to-white IRR 1.55). Black patients with CTCL were diagnosed at a younger age and black patients with MF/SS presented with advanced stage and had worse survival than white patients. In multiple-variable Cox-regression models, age > 60 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.97–7.70), black race (HR 2.09, 95% CI 1.29–3.37) and advanced stage (HR 6.06, 95% CI 3.66–10.05) predicted worse survival for patients with MF/SS. Additional research identifying reasons for these differences are necessary to better understand these diseases and for new strategies in the treatment of CTCL.

A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma

To define the clinicopathologic and prognostic features of patients with human T‐cell lymphotropic virus type‐1 (HTLV‐1)‐associated adult T‐cell leukemia/lymphoma (ATLL) in North America, standard criteria were used to identify patients with ATLL.

A multi-institutional experience of autologous stem cell transplantation in North American patients with human T-cell lymphotropic virus type-1 adult T-cell leukemia/lymphoma suggests ineffective salvage of relapsed patients

Department of Medicine, Division of Hematology/Oncology, College of Physicians and Surgeons, Columbia University, New York, NY, USA, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Division of Hematology/Oncology, Department of Medicine, Bone Marrow Transplantation Program, Mount Sinai Medical Center, New York, NY, USA, and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA

Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma

An increased risk of non‐Hodgkin lymphoma (NHL) has been observed among individuals with occupational exposure to benzene, but the risk among those living near benzene release sites has not been well described.

Real-time PCR-based analysis of BRAF V600E mutation in low and intermediate grade lymphomas confirms frequent occurrence in hairy cell leukaemia.

Hairy cell leukaemia (HCL) is a rare type of B‐cell non‐Hodgkin lymphoma (B‐NHL), which is not known to be associated with any characteristic recurrent karyotypic abnormality. A recent study that used massively parallel whole exome sequencing identified an activating V600E mutation in BRAF, which appeared specific for HCL. Here, we confirm the specificity of BRAF V600E for HCL among low and intermediate grade B‐NHL and describe a real‐time polymerase chain reaction method for detecting this mutation in cases with low tumour burden. The V600E mutation does not appear to be associated with microsatellite instability, unlike the case in colorectal cancer. Thus, in conjunction with prior data, our results suggest incorporation of BRAF V600E mutation analysis in the diagnostic workup of HCL cases. Additionally, targeting the Ras‐Raf‐Mek‐Erk‐Map kinase pathway should be investigated as a potential therapeutic strategy for patients with this disease. Copyright

Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma

Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma

Cord blood chimerism and relapse after haplo-cord transplantation

Abstract Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18–72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p < 0.0001) and decrease in one year progression-free (20% versus 55%, p = 0.004) and overall survival (30% versus 62%, p = 0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p = 0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p = 0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.

Haplo-cord transplant: HLA-matching determines graft dominance

Haplo-cord transplantation combines the infusion of CD34 selected third party cells from a haplo-identical donor, with an umbilical cord blood (UCB) graft from an unrelated donor.[1–5] In a majority of the cases, initial engraftment from the haplo-identical donor is superseded by dominance of the UCB graft. But in some cases, only the haplo-graft persists. In previous studies, we found that patients who received very high CD34 doses from the haplo-identical donor had impaired/delayed UCB engraftment.[6] More recently, we have limited the cell dose of the haplo-graft to 3–5 10 CD34/kgrec. But occasional cases of haplo-dominance continue to occur. Here we attempted to determine the additional graft and conditioning characteristics that influence the interaction between haplo-graft and cord blood graft and the eventual long-term dominance of one graft over the other. All the patients were enrolled in a prospective study of reduced intensity conditioning and haplo-cord transplantation. The study was approved by the Institutional Review Board of Weill Cornell Medical College and all patients and donors provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and registered on clinical trials.gov (NCT01810588). Cord blood units (CBUs) were selected based on human leukocyte antigen (HLA) typing and cell count. As of mid-2012, we utilized high-resolution HLA typing for HLA-A, B, C, and DR for cord graft selection.[7] In contrast with common practice, we prioritized matching over cell dose and established a minimum cell count of 1.2 10 nucleated cells/kg of the recipient’s body. After collection and prior to cryopreservation, haploidentical grafts were T-cell depleted using the Miltenyi CliniMACS device under an Investigational New Device (IND) permit from the United States Food and Drug Agency. The infused cell dose of the haplo-graft was fixed at a minimum of 3 10 CD34 cells/kg and a maximum of 5 10 CD34 cells/kg of recipient weight. Patients received fludarabine 30mg/m/d iv for 5 consecutive days (days 7, 6, 5, 4, 3), rabbit antithymocyte globulin (thymoglobulin, r-ATG) at 1.5mg/kg every other day for 3 or 4 doses, and melphalan 140mg/m/d for 1 dose on day 2.[8] Thirteen patients were also given a 400 cGray, usually because of concern over disease recurrence. One patient received TBI 600 cGray. The haplo-identical cells were infused on day 0 followed by cord blood later the same day or on day 1. Posttransplant GVHD prophylaxis consisted of tacrolimus on day 2 until day 180 and mycophenolate mofetil 1 g per oral (po) three times a day (TID) until day 28. CD3 and CD33 chimerism was studied as previously described.[9] Univariate regression models were used to analyze the relation between continuous variables and chimerism. T-tests or ANOVA were used for categorical variables. All p values are two-sided. Factors examined include (1) degree of CBU HLA-match to recipient dichotomized as 4-5-6 out of 8 HLA match vs. 7 or 8 out of 8 HLA match, (2) UCB graft CD34/kgrec collected, (3) UCB TNC/kgrec infused, (4) presence of donor-specific antibodies (DSA) against UCB graft, (5) UCB viability at the time of infusion – as defined by >90% Trypan blue exclusion vs. <90%, (6) degree of haplo-graft HLA-match to recipient HLA-dichotomized as 4–5 out of 8 HLA match vs. 6–7 out of 8 HLA match, (7) presence of DSA against haplograft, (8) use of TBI in conditioning, (9) CIBMTR Disease Risk index, (10) degree of HLA match between CBU and recipient, (11) degree of HLA match between haplo-graft and recipient, and (12) degree of HLA match between CBU graft and haplo-graft. Eighty-three patients with hematologic malignancies were enrolled between January 2012 and February 2015. Four died prior to engraftment including one due to infection, one from multi-organ failure, and two from VOD/SOS. Of the remaining 79 patients, three (4%) had complete graft failure with autologous reconstitution. Seventeen additional patients were excluded from the

The Addition Of Low Dose Total Body Irradiation To Fludarabine And Melphalan Conditioning In Haplo-Cord Transplantation For High Risk Hematological Malignancies.

Background Preliminary evidence indicates that the addition of low-dose total body irradiation (TBI) (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high-risk patients receiving combination haploidentical single-unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. Methods We retrospectively reviewed the posttransplant outcomes of patients who underwent haplocord stem cell transplant between May 2013 and March 2015 and who received fludarabine 30 mg/m2 day (D)−7 to −3, melphalan 140 mg/m2 D−2, and 2 Gy TBI D−4 and −3. Results All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of nonrelapse mortality was 16% by D+100 and 33% by 1 year. The cumulative incidence of grade III to IV acute graft-versus-host disease was 36% by D+100. The CIR was 13% by D+100 and 29% by 1 year. The estimated 1-year overall survival and progression-free survival were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 acute myeloid leukemia patients receiving this conditioning regimen with age and disease risk index–matched acute myeloid leukemia patients receiving fludarabine-melphalan without TBI. The TBI group had lower incidence of relapse at 1 year (15% vs 54%, P = 0.05). Conclusions Overall, combination fludarabine-melphalan with low-dose TBI after haplocord stem cell transplant assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.