Olga Derman

Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study.

BACKGROUND The attacks on the World Trade Center (WTC) on Sept 11, 2001 (9/11) created the potential for occupational exposure to known and suspected carcinogens. We examined cancer incidence and its potential association with exposure in the first 7 years after 9/11 in firefighters with health information before 9/11 and minimal loss to follow-up. METHODS We assessed 9853 men who were employed as firefighters on Jan 1, 1996. On and after 9/11, person-time for 8927 firefighters was classified as WTC-exposed; all person-time before 9/11, and person-time after 9/11 for 926 non-WTC-exposed firefighters, was classified as non-WTC exposed. Cancer cases were confirmed by matches with state tumour registries or through appropriate documentation. We estimated the ratio of incidence rates in WTC-exposed firefighters to non-exposed firefighters, adjusted for age, race and ethnic origin, and secular trends, with the US National Cancer Institute Surveillance Epidemiology and End Results (SEER) reference population. CIs were estimated with overdispersed Poisson models. Additional analyses included corrections for potential surveillance bias and modified cohort inclusion criteria. FINDINGS Compared with the general male population in the USA with a similar demographic mix, the standardised incidence ratios (SIRs) of the cancer incidence in WTC-exposed firefighters was 1·10 (95% CI 0·98-1·25). When compared with non-exposed firefighters, the SIR of cancer incidence in WTC-exposed firefighters was 1·19 (95% CI 0·96-1·47) corrected for possible surveillance bias and 1·32 (1·07-1·62) without correction for surveillance bias. Secondary analyses showed similar effect sizes. INTERPRETATION We reported a modest excess of cancer cases in the WTC-exposed cohort. We remain cautious in our interpretation of this finding because the time since 9/11 is short for cancer outcomes, and the reported excess of cancers is not limited to specific organ types. As in any observational study, we cannot rule out the possibility that effects in the exposed group might be due to unidentified confounders. Continued follow-up will be important and should include cancer screening and prevention strategies. FUNDING National Institute for Occupational Safety and Health.

Adult T-cell leukemia/lymphoma in the Caribbean cohort is a distinct clinical entity with dismal response to conventional chemotherapy

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive disease caused by human T-cell lymphotropic virus type 1 that predominantly affects Japanese and Caribbean populations. Most studies have focused on Japanese cohorts. We conducted a retrospective analysis of 53 cases of ATLL who presented to our institution between 2003-2014. ATLL in the Caribbean population presents more often as the acute and lymphomatous subtypes, is associated with complex cytogenetics, and has a high rate of CNS involvement. The overall response rate to first-line therapies with anthracycline-based regimens was poor (32%), with a median survival of only 6.9 months. A complete or partial response to first-line regimens was associated with better survival. There was no difference in survival between patients who received chemotherapy alone versus chemotherapy with antiviral agents. Allogeneic transplantation was performed in five patients, two of whom achieved complete remission despite residual or refractory disease. Recipients of allogeneic transplantation had significantly improved overall survival compared to non-transplanted patients. This is the first analysis to describe ATLL pathological features, cytogenetics, and response to standard therapy and transplantation in the Caribbean cohort.

Analysis of chronic myelogenous leukemia in an underserved, inner-city cohort shows a significant five year overall survival that is not affected by choice of tyrosine kinase inhibitor

Tyrosine kinase inhibitors (TKIs) have become the firstline treatment of choice for chronic myelogenous leukemia (CML) after imatinib was shown to offer improved and durable responses.[1,2] Second generation TKIs such as nilotinib [3,4] and dasatinib [5,6] have shown superior efficacy in achieving faster remissions in the first-line setting. Patients who achieve a complete cytogenetic response at two years have a life span similar to that of the general population as long as they receive adequate therapy and adhere to treatment.[7] Despite efficacy, the cost of TKIs created a significant financial burden which led leaders in the field to speculate on whether such prices are justifiable.[8] Individuals with ‘adequate’ healthcare coverage are not immune and may have a 20% out of pocket co-payment. Adherence to therapy is essential to achieve adequate responses.[9] Higher socioeconomic status was linked to better imatinib adherence [10] and patients with higher copayments were more likely to have poorer adherence.[11] To examine the impact of cost of TKIs on efficacy, we conducted a retrospective analysis to determine the treatment patterns in an inner-city population comprised predominantly of ethnic minorities with low socioeconomic status. We aimed to study access to different generations of TKI, reasons for switching TKIs as well as overall survival (OS). We included CML cases that presented to Montefiore Medical Center between 1997 and 2014 in the Bronx, New York. Cases were identified by a data-mining software (Clinical Looking Glass , CLG) used to search by ICD-9 diagnosis code. Records were manually reviewed to confirm diagnosis and to collect relevant demographic and CML-specific data. The population number (n value) was adjusted to reflect the number of records with available data pertaining to each variable. As such, the number of evaluable records for phase at diagnosis, first-line therapy, line of therapy at the conclusion of the study, and line of therapy at expiration was 77, 118, 125, and 20 patients, respectively. All chart review was conducted by one of the study authors and discrepancies were reviewed by at least two authors. This research was approved by our institutional review board and ethics committee. For comparison, we obtained data from the Surveillance, Epidemiology and End Results (SEER) program database. SEER collects cancer incidence, treatment, and survival information from 18 geographic areas in the United States, representing 28% of the entire population. We used direct case listings extracted by SEER*Stat software (version 8.1.5, released March 31, 2014) and included patients with a diagnosis of CML with the International Classification of Disease for Oncology, third edition, ICD-0-3 histology code 9863, 9875, 9876, 9945, 9946 until the latest follow-up recorded in the SEER submission. For analysis of categorical variables, we reported proportions and p values calculated with Pearson chi square or Fisher exact test as appropriate. Kaplan–Meier curves were used to compare survival and significance was examined using the log rank test. Statistical analyses were performed with computer software (SPSS 18, SPSS, Inc., Chicago, IL) and a two-tailed alpha of 0.05 was used to denote significance.

Response of Paroxysmal Nocturnal Hemoglobinuria Clone with Aplastic Anemia to Rituximab

Paroxysmal nocturnal hemoglobinuria is caused by expansion of a hematopoietic stem cell clone with an acquired somatic mutation in the PIG-A gene. This mutation aborts the synthesis and expression of the glycosylphosphatidylinositol anchor proteins CD55 and CD59 on the surface of blood cells, thereby making them more susceptible to complement-mediated damage. A spectrum of disorders occurs in PNH ranging from hemolytic anemia and thrombosis to myelodysplasia, aplastic anemia and, myeloid leukemias. Aplastic anemia is one of the most serious and life-threatening complications of PNH, and a PNH clone is found in almost a third of the cases of aplastic anemia. While allogeneic bone marrow transplantation and T cell immune suppression are effective treatments for aplastic anemia in PNH, these therapies have significant limitations. We report here the first case, to our knowledge, of PNH associated with aplastic anemia treated with the anti-CD20 monoclonal antibody rituximab, which was associated with a significant reduction in the size of the PNH clone and recovery of hematopoiesis. We suggest that this less toxic therapy may have a significant role to play in treatment of PNH associated with aplastic anemia.

Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G-CSF in multiple myeloma: A pilot study

Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G-CSF resulted in improved HSC mobilization. Here, we present the results of an open-label single-arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G-SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G-CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G-CSF administration (D-3) and continued taking it along with G-CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G-CSF is safe and signals improved mobilization over G-CSF alone, providing a possible alternative means of mobilization that needs further investigation.

Characteristics and outcomes of progressive multifocal leukoencephalopathy in hematologic malignancies and stem cell transplant – a case series

Abstract Progressive multifocal leukoencephalopathy (PML) is a life-threatening opportunistic infection of immunomodulatory therapies. PML cases reported in PubMed (1995–2017) following stem-cell transplantation (HSCT) or chemoimmunotherapy (CIT) for hematologic malignancies were reviewed. We found 107 cases, 40% were HSCT recipients (32 allogeneic, 11 autologous) and 40% indolent lymphomas receiving monoclonal antibodies (mAbs). HSCT cases had longer time to PML diagnosis (10.8 vs. 4 months, p < .001), higher proportion of PML therapy response (58% vs. 25%, p = .019), lower mortality rate (56% vs. 88%, p < .001), and longer median survival (8 vs. 2 months, p < .001). Outcome differences might be caused by selection bias as HSCT patients are most likely treated aggressively; however, time-dependent immune reconstitution might also contribute to their better prognosis. Increased use of mAbs and HSCT are associated with rising PML incidence in hematological malignancies, currently constituting the second largest vulnerable population after HIV-infected patients; further research is needed for its optimal treatment.

Ibrutinib-induced severe liver injury

Ibrutinib, an inhibitor of the Brutons tyrosine kinase of the B‐cell receptor pathway, is an effective therapeutic agent for B‐cell lymphomas. As these drugs are novel, long‐term or rare adverse events are not yet known. We report the first case of ibrutinib‐induced severe liver injury in a patient with relapsed/refractory CLL.

Hispanic ethnicity is associated with younger age at presentation but worse survival in acute myeloid leukemia

SEER data and a Bronx validation cohort demonstrate that Hispanics present with AML at younger age but have shorter survival than whites.Increased frequency of high-risk mutations in Hispanics provides a potential biologic explanation for poorer outcomes in Hispanics.