We describe a case of a 63-year-old woman with advanced colon cancer and liver metastases who was treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and cetuximab chemotherapy. She tolerated 13 cycles of chemotherapy without any significant hematological side effects, but after the 14th cycle, she developed melena and was admitted for severe thrombocytopenia. After supportive care, the platelet counts rapidly improved to 76,000/μL. Upon initiation of FOLFIRI and cetuximab chemotherapy, she again developed rectal bleeding and severe thrombocytopenia with a platelet count of 6000/μL. Lab testing was positive for oxaliplatin and irinotecan drug-dependent platelet antibodies on flow cytometry assay. Drug-induced thrombocytopenia (DITP) is associated with several classes of drugs with several proposed underlying mechanisms. Prospective studies are needed to further address different mechanisms of drug-induced thrombocytopenia.

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.

Background: RBC size variation and microcytes in B12D are often ascribed, but rarely shown, to be due to co-existing Fe deficiency. Schistocytes (aka poikilocytes) were included in early descriptions of pernicious anemia (PA). As it also causes thrombocytopenia, B12D may be confused with thrombotic thrombocytopenic purpura (TTP). Because of the urgency of PP for TTP, it has sometimes been initial therapy for B12D with schistocytes. Purpose: Here we describe 3 PA patients, and review reports of 15 other severely anemic B12D cases, with schistocytes. As they are smaller than mature RBC, they may normalize the MCV, while raising the RDW. We wished to determine whether primary lab studies help to distinguish B12D from TTP. Case Reports: These patients presented with symptoms of severe anemia: Ferritins were normal or high, haptoglobins <30, anti-intrinsic factor and parietal cell antibodies present, and complete response to B12 therapy occurred. Significant numbers of schistocytes were present in all, as was a distinctive population of minute, hypochromic schistocytes (MHS). Review: We found 15 reports of individual B12D patients with schistocytes, published between 2003 and 2015. All but 2 vegans had PA, 6 being anti-IF Ab+. Median & median ages were 52 & 53, [Hb]'s 5.9 & 6.0, MCV's 120 & 117 (3 normal), platelets 97 & 85, WBC 3200 & 3120, LDH's 4050 & 5860; reticulocyte levels were all low for severe anemia. Iron deficiency anemia was not found; ferritin and/or Fe/TIBC were reported normal in 4. Six legible blood smear microphotographs were included, confirming schistocytosis. Five patients had one or more PP before B12 deficiency was discovered. All 15 responded completely to B12. MHS were also observed on 4 of the 6 legible microphotographs, and noted by authors. For comparison, our survey of 36 reported TTP legible blood smears failed to detect MHC. Conclusions: Schistocytes are observed in some severely anemic B12D, may account for as much as 6.7% of RBC, and alter their indices. Schistocytosis and thrombocytopenia suggest TTP, and may lead to unnecessary PP. But such patients' low reticulocyte counts and very high LDH levels are not typical of TTP. Table Table. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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 StudyATL is a rare and aggressive peripheral T-cell neoplasm characterized by clonal human T-cell lymphotropic virus type-1 (HTLV-1) proviral DNA integration with host T lymphocytes.These patients commonly present with lymphadenopathy, skin rash, fever, fatigue or altered mental status. The prevalence of CNS disease varies from 3 to 50% and is always in the presence of systemic disease. Isolated cranial neuropathy as a presenting symptom has not been described in literature.Methods UsedRetrospective chart review and review of literature.Summary of Results49 year old Caribbean male presented with 2 month history of left sided headache, 5 weeks of right sided jaw numbness and pain which progressed to contralateral side. He was now unable to smile and had food falling from the side of his mouth. He denied fever, fatigue, night sweats, rash, weakness or abnormal lumps. He had normal mental status and good motor strength. Facial exam reveal bilateral upper and lower facial paralysis, left lateral rectus palsy and horizontal gaze diplopia. Rest of the physical exam was unremarkable. Labs revealed WBC of 6 k/mm3 with normal differential, HB 16.5 gm/dl and platelets 238 k/mm3. Complete metabolic profile and peripheral smear was normal. MRI Brain showed irregular, fusiform enhancement of left trigeminal nerve, bilateral facial and abducent nerves. CSF flow cytometry showed clonal CD4+ CD25+ T cell population. HTLV-1 serology was reactive. Left infraorbital nerve biopsy confirmed involvement with ATL. CT Chest/abdomen/pelvis did not reveal enlarged lymphadenopathy. He was started on treatment with EPOCH and twice weekly intrathecal methotrexate for 4 months with clearance of CNS fluid. His jaw pain and vision improved but facial nerve paralysis persisted. He developed local relapse four months after treatment and was treated with high dose methotrexate for 5 cycles. Ultimately his performance status deteriorated and he succumbed to the disease progression.ConclusionsThis case illustrates the unique presentation of this disease and gives an insight on one treatment approach. This patient achieved remission with our approach of aggressive chemotherapy with intrathecal methotrexate although the duration of remission was short lived.

Purpose of StudyTo demonstrate the presence and attributes of microcytes in Pernicious Anemia (PA) patients with high Red blood cell (RBC) distribution widths (RDW), but without iron deficiency or thalassemia trait. Marked macrocytosis is typical of PA, but their RDW are usually elevated (>21%).Methods Used Cases and MethodsWe report two patients with severe anemia, B12 deficiency, and elevated RDW's.Patient 1: 55 y/o African–American man, with dyspnea, finger paresthesias without gait disturbance. WBC 2.4 K/uL, Hb 4.8 g/dL, MCV 84.8 fL, RDW 30%, reticulocyte count 15 K/uL, iron 234 µg/dL, ferritin 880 ng/dL, platelets 70 K/uL, LDH 5980 U/L, B12 <30 pg/mL.Patient 2: 37 y/o African-American woman with long hx of anemia, recent weakness, and gait disturbance. WBC 3.5, Hb 6.3, MCV 114, RDW 29.5%, reticulocyte count 27, iron 108, TIBC 304 mg/dL, ferritin 50, platelets 45, LDH 2484, B12 60.Both patients' hematologic parameters normalized within 1–7 months after B12 treatment.Summary of ResultsMicrocytes constituted 32.8% of 1000 RBC in patient 1, whose MCV was normal, and 19.3% in patient 2. They were minute, irregular or twisted cells, often with two very unequal dimensions. They were often normochromic, or even hypochromic. Twenty of the small cells were measured, and their smallest dimension ranged from 2–4 microns, with an average of 3.0 microns. The larger dimension averaged 1.5–2.0 times greater than the smaller. The larger cells were circular or elliptical, with equal dimensions ranging from 6.2 to 13 microns.ConclusionsAlthough the coexistence of macrocytic and normocytic RBC may help to explain PA patients' high RDW, a significant percentage of their RBC may be microcytic. These microcytes are smaller than those in iron deficiency or thalassemia, have very irregular shapes (micro-poikilocytes), and resemble neither other types of microcytes nor schistocytes. The microcytes in one patient reduced his MCV to a normal level. These microcytes may be the result of megaloblastic dyserythropoiesis.