Background: Apheresis can be associated with adverse events (AEs). Available studies published on apheresis-associated AEs lack uniformity of data. Unfortunately, there is no common database in the United States (US) to report apheresis-associated AEs. We evaluated our institutional incidence of apheresis-associated AEs and compared it with published literature. Study design and methods: We conducted a 10-year retrospective study of apheresis procedures and associated AEs at our facility, a tertiary academic medical center, from 2007 to 2016. Concurrently, a literature search was conducted on AEs associated with apheresis procedures. Twenty-eight studies including data from US and other countries' facilities were analyzed. Results: The overall AE incidence was 6.9% (396/5684 procedures). Frequency of AEs associated with therapeutic plasma exchange (TPE) was higher (8.5%, P < .0001) compared to other apheresis procedures. Significant correlation between number of TPE and AEs (Spearman rho [r s ] = 0.7, P = .002) was encountered.Furthermore, there was a significant decrease over time of moderate and severe AEs (r s = −0.64, P = .04 and r s = −0.83, P = .003 respectively). Comparison of our institutional AEs (6.9%) to data from other countries (9.8%) and US (22.6%) indicated a significant difference (P < .0001). Conclusion: Overall our incidence of AEs was significantly lower than current published literature. Incidence of AEs published in other countries is significantly lower than US rates. Differences in incidence of AEs emphasize need for uniform reporting and stratification of AEs and development of a common database to report AEs. Therefore, we propose a grading rationale in order to standardize reporting of AEs. K E Y W O R D S adverse events, apheresis, complications, hematopoietic stem cell collection, red cell exchange, therapeutic plasma exchange

BackgroundMultiple myeloma (MM) is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here.MethodsThis retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood. Data from patients diagnosed with MM from 2000 through 2013 were collected from the institution’s tumor registry. Clinical and demographic characteristics of these patients were then analyzed.ResultsPatients with a diagnosis of MM were identified (N = 287). Data were available for 231 patients and of these, 97% self-identified as black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean age of female patients was 64 years; that of male patients was 63 years. Of the 231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and 29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of patients and 57% had disease of International Staging System stages I and II. Women had higher BMI than men.ConclusionThe mean age of presentation of MM in Afro-Caribbean patients is similar to that in the standard population; however, unlike the general US population, there was a higher incidence in women; mean BMI of women also was higher than that of male patients. A sizeable percentage of Afro-Caribbean patients with MM presented with low levels of monoclonal protein in the presence of multiorgan involvement and damage, suggesting the need for early and aggressive diagnostic testing.

Purpose of StudyAutoimmune hemolytic anemia (AIHA) is a common phenomenon in Chronic lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) accounting for about 4–7% of cases. AIHA is commonly associated with certain conventional chemotherapy agents used in CLL/SLL. Ibrutinib, bruton tyrosine kinase inhibitor is category 1 indication for high risk (del 17p) and relapsed/refractory CLL. Literature review reports 11cases of Ibrutinib associated AIHA.We report a case of AIHA precipitated by Ibrutinib in an high risk CLL patient, with prior history of AIHA.Methods UsedPatient is an 81 year old black man diagnosed with asymptomatic Stage I CLL (del 17p) in 2010 and was on active surveillance. He developed AIHA in 2012, with good response to steroids and Rituximab. Subsequently he received 8 cycles of rituximab for symptomatic CLL with resolution of symptoms. In 9/2014, noted to have progression of disease with worsening B symptoms, leukocytosis and lymphadenopathy. He was started on Ibrutinib 420 mg PO daily with regression of lymphadenopathy within 3 weeks of therapy, but presented with symptomatic anemia with hemoglobin of 3 gm/dl, positive direct Coomb's test, elevated reticulocyte count and LDH consistent with AIHA. WBC elevated at 360 K/uL from baseline of 150 K/uL and hemoglobin fell to 3 g/dl from 10 g/dl since Ibrutinib was initiated. Ibrutinib was held and patient received high dose prednisone followed by IVIG and cautious transfusion with minimal improvement in hemoglobin. Hemoglobin slowly up trended with weekly Rituximab and high dose steroids and remained stable around 10 gm/dl after 4 weeks of Rituximab. Ibrutinib was subsequently restarted with overall clinical improvement.Summary of ResultsIn our patient, occurrence of AIHA falls in between 2–4 weeks as other reported cases suggesting that Ibrutinib could be a likely precipitating factor.ConclusionsReview of data, reveals that 22% of patients had history of AIC prior to Ibrutinib, however occurrence of AIHA on Ibrutinib seems to be less common (0.7%).Mechanism of action of Ibrutinib associated cytopenias remains unclear. It was hypothesized that it may be due to IL-2 induced kinase inhibition by Ibrutinib, and needs further investigation.

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of monoclonal immunoglobulin (Ig), without the diagnosis of multiple myeloma (MM), while the diagnosis of MM requires the presence of a monoclonal immunoglobulin (Ig) ≥ 3g/dl or Bence-Jones protein (BJP) ≥ 500mg/24h, with bone marrow involvement of greater than 10% clonal plasma cells. Kings County Hospital (KCH) is an institution that serves a large population of Afro-Caribbean population. In our institution, an increased number of patients were observed to present with MM with monoclonal Ig <3g/dl but yet have end organ damage. The clinical characteristics of Afro-Caribbean population have not been well studied and further characterization may have diagnostic implications. Methods This is a retrospective study conducted at KCH. Data regarding the clinical profile of patients diagnosed with MM from 2000- 2013 was collected from the institution's tumor registry. Patients with monoclonal Ig < 3g/dl and BJP <500mg/24h were analyzed and compared to standard MM patients with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. Data was collected for lab parameters which included quantity and type of monoclonal Ig, serum free light chains and ratio, monoclonal plasma cell percentage in the bone marrow, International staging system (ISS) stage, cytogenetics, presence of anemia, hypercalcemia, renal failure and lytic lesions. Epidemiologic parameters age and gender were also collected. Results were analyzed by a Chi-square test to calculate a mid-P exact. Results A total of 287 patients with MM were screened, of which 56 patients with incomplete electronic records were excluded. Of the remaining 231 patients, 63 (27%) had monoclonal Ig <3 g/dl without the presence of BJP ≥ 500mg/24h. These patients were labeled hyposecretory MM. 168 (73%) patients had standard MM, with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. In the hyposecretory MM group, 35% of patients presented with International staging system (ISS) stage I vs. 13% in the standard MM group (P= 0.0001). IgG monoclonal Ig was present in 75% of patients with hyposecretory MM compared to 62% in the standard MM group (P=0.04). Mean plasma cell percentage in the bone marrow was similar in both groups, 40% in the hyposecretory MM group compared to 51% in standard MM. Average age of presentation was 64 yrs in the hyposecretory MM group as compared to 63 yrs in the standard MM group. There were more females than males in both groups, 61% females in hyposecretory MM and 53% in standard MM group. The most common presenting symptom was anemia in both groups and there were no statistically significant differences noted in gender, presence of hypercalcemia, presence of bone lesions, and renal dysfunction. Cytogenetic data was insufficient. Conclusion In our study, a substantial number of Afro-Caribbean patients with low levels of serum monoclonal Ig without the presence of Bence-Jones protein were diagnosed with active multiple myeloma. The results of our study underline the importance of an aggressive diagnostic approach with a bone marrow biopsy at initial presentation with MGUS in Afro-Caribbean population. This may prevent disease progression and end organ damage. Unlike the general population with MM, there were more females. Disclosures No relevant conflicts of interest to declare.

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Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer (BrCa) of which 12,000 individuals carry BRCA germline mutations. MicroRNA dysregulation is common in malignancy and may correlate with germline mutations.Aims:1. Analyze microRNAs in patients with breast cancer with or without BRCA germ line mutations, with and without cancer.2. Identify molecular BRCA mutant patients to deduct reasons for accelerated malignancy.Methods UsedWe analyzed plasma miR expression from 94 br cancer patients (41 BRCA positive) relative to 24 normal controls. All samples were collected between 2010 and 2014 and survival data was known for all cancer patients. TaqMan Open Array panel was used to simultaneously run hundreds of microRNA assays in the Applied Biosystem Open array real time PCR. Using AB open array real time PCR, 756 miRNA species were detected. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Tukey HSD post-hoc test to compare the miRs mean differences. All tests were 2-tailed and results with a p<0.05 were considered statistically significant.Summary of ResultsBRCA+underexpressed hsa-mir-10a and hsa-mir-376c and over-expressed Hsa- mir- 326 and Hsa-mir-143 relative to BRCA-; p<0.05.Using Coremine data mining linking genes and diseases differentially expressed circulating miRs are linked to tumor suppressor TGFbeta/SMAD3.ConclusionsThe early onset of breast cancer in BRCA mutant patients may recapitulate the pro-oncogenic effects of TGF-β. The context dependent SMAD3 binding & tumor suppression TGF-β effects are abrogated in BRCA mutant patients. TGF-β/Smad3 tumor-suppressor signature suppresses local inflammation in the tumor microenvironment.

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