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 Hemophilia C or factor XI deficiency is a rare clotting disorder with prevalence of only 1 per 1 million. A 24-year-old male with multiple abdominal surgeries complicated by wound infections and poor healing was admitted to plastic surgery service for an elective abdominoplasty. Hematology was consulted for increased intraoperative and postoperative bleeding. Laboratory workup showed high-normal activated plasma thromboplastin time of 31 s (reference: 23 - 34 s), prothrombin time (PT) of 15 s (reference: 11.8 - 14.3 s) and internationalized normal ratio (INR) of 1.2. Patient had normal factors VIII, IX, XIII levels and normal von Willebrand's factor level. The factor XI level came back at 0.28 (0.44 - 1.43 U/mL) diagnostic for intermediate factor XI deficiency. Factor XI is responsible for thrombin generation after clotting is initiated as well as clot stabilization. The confirmatory test is factor XI assay. The management of factor-XI deficiency is based on history of bleeding and nature of the procedure. J Hematol. 2019;8(3):144-147 doi: https://doi.org/10.14740/jh522 Â

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation and immune activation. The syndrome can be triggered by multiple events that disrupt immune homeostasis, including infection, autoimmune diseases, and lymphoma. Although more common in children—which might indicate a genetic cause—HLH can occur in patients of any age. The most common presenting features of HLH are fever, cytopenia, hepatitis, and splenomegaly. Other features include neurologic abnormalities such as altered mental status, seizures, and ataxia. It is a reactive process of antigen-presenting macrophages and CD8+ T‑cell activation and migration. In addition, abnormalities in the action or number of natural killer cells have been observed. Direct cytotoxicity from T cells, along with elevated levels of pro-inflammatory cytokines and interleukins, plays a role in the generation of excessive inflammation that leads to organ dysfunction. We present the case of a 61-year-old female patient with a past history of recurrent self-limiting episodes of fever that occurred two to three times every autumn for the past 11 years. The meticulous thought process that led to her diagnosis with HLH and marginal zone lymphoma is discussed.

Historically known to be a disease of sailors and soldiers in the seventeenth and eighteenth century, scurvy is a rare nutritional deficiency in the developed world, but it can still be seen among the alcoholics and the malnourished. We present a case of a 39-year-old alcoholic male who presented with progressive fatigue and diffuse purpuric rash with scattered ecchymosis for 2 months. Blood work was remarkable for hemoglobin of 9.1 g/dl, which further dropped to 7 g/dl over the next few days. He was then found to have hemolysis on lab work. After an extensive workup, the common causes of hemolytic anemia were ruled out, vitamin C level was checked, which interestingly resulted as 0 mg/dl. Supplementation with oral vitamin C resulted in the gradual resolution of hemolytic anemia and rash. Hemoglobin improved to 15 g/dl in 4 weeks, with normalization of vitamin C level. The clinical features of scurvy can easily be confused with conditions such as vasculitis, deep venous thrombosis, and systemic bleeding disorders. Therefore, comprehensive workup up is required prior to the diagnosis. Although rare, being a reversible condition, early diagnosis and treatment of scurvy in high-risk populations cannot be stressed enough.

Introduction. Senile systemic amyloidosis is a multisystem disease where wild-type insoluble transthyretin (ATTRwt) protein gets deposited in the tissues leading to organ dysfunction. Methodology. We present the case of a patient who presented with hematuria and bladder involvement by ATTRwt amyloidosis who ultimately died of multiorgan failure. Results. The patient was an 82-year-old white male with a history of ischemic cardiomyopathy (ejection fraction (EF): 20–25%), chronic atrial fibrillation, chronic kidney disease (CKD), and carpal tunnel syndrome who presented with acute hematuria, urinary retention, and progressive fatigue. He underwent cystoscopy and bladder biopsy which was positive on congo-red stain diagnostic for amyloidosis. Echocardiogram demonstrated worsening of EF to 10–15% and concentric left ventricle hypertrophy. MRI was not performed due to underlying CKD. His condition deteriorated during the hospital stay, and he developed cardiogenic shock and progressive liver dysfunction. Infectious workup was negative. Meanwhile, the biochemical investigations (serum protein electrophoresis, immunofixation, and urine kappa/lambda chains) ruled out plasma cell dyscrasias. Mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) amyloidosis consistent with senile systemic amyloidosis. Due to patients’ extremely poor prognosis, his family wished to focus on patient’s comfort-oriented measures only, and patient passed away shortly thereafter. Conclusion. Senile systemic amyloidosis can rarely present in an atypical fashion such as hematuria. The treatment options are limited in this disease process. Novel therapies are in the early phases of development. Concern also exists that in patients with multiple comorbidities, this entity is under recognized until the more advanced stages.

Introduction. Glanzmann’s thrombasthenia is a rare clotting disorder caused by impaired platelet function. Lack of awareness of the appropriate management of rare medical conditions may lead to patient dissatisfaction and potentially poor treatment outcome. Case Report. A 78-year-old male with a history of Glanzmann’s thrombasthenia was admitted to the trauma service following a fall in which he sustained a facial laceration as well as maxillary sinus and nasal fractures. He received DDAVP 20 mcg and tranexamic acid upon presentation to the emergency department (ED). In the ED, the patient requested administration of platelet transfusion but was refused due to a normal platelet count. During the course of his hospital stay, he complained of epistaxis and was noted to have a downtrending hemoglobin from 11.0 g/dl to 9.0 g/dl. The patient and his family were not comfortable when the discharge plan was finalized and demanded platelet transfusion (due to history of needing platelets in association with injuries or procedures in the past) was refused by the primary team as they continued to state that his platelet count is normal. On hospital day 3, hematology was consulted as the patient and his family were extremely angry and hematology recommended platelet transfusion. Further clinical information was not available as the patient was transferred to another facility per family request as they wanted to be at a center which had the patient’s primary hematologist. Discussion. A delay in specialist consultation resulted in patient dissatisfaction and extended the length of stay. Patients with rare medical conditions and potential for major complications should be managed aggressively with appropriate specialist consultation to promote patient satisfaction and improve the overall quality of care. This case shows that as physicians it our duty to listen to our patient’s concerns and involve them in the medical decision-making to provide optimal patient-centered care.

Mantle cell lymphoma (MCL) is a form of non-Hodgkin’s lymphoma originating from mature B cells. The hallmark gene translocation (11:14) results in overexpression of cyclin D1. Affected extranodal sites include bone marrow and gastrointestinal tract, but skin, orbit or CNS are rarely involved. Twenty-four cases have reported involvement of skin by MCL, while orbital MCL is equally rare. Our case is the first to report relapsed MCL with involvement of the skin and orbit simultaneously without disease in the lymphatic system or the bone marrow. A 53-year-old female with stage IV MCL initially presented with pancytopenia, adenopathy and splenomegaly. She achieved complete remission after six cycles of rituximab and bendamustine. Within 4 weeks of treatment, she developed diplopia and a rash of the left breast. Skin biopsy showed lymphoma infiltrates with B-cell markers for MCL. MRI of the orbits and brain suggested orbital lymphoma. CSF cytology further confirmed MCL cells. At time of relapse, she continued to be in hematologic remission. She initiated intrathecal cytarabine and methotrexate along with ibrutinib. R-CHOP was then added to the regimen. Within 2 weeks of starting treatment, her skin disease resolved and she had improvement in vision. MCL commonly presents as a disseminated disease, resulting in high mortality. Involvement of the skin or orbit has been sparingly reported and always suggests aggressive disease. It thus poses a challenge to diagnose and treat the condition as evidenced by resolution of adenopathy and bone marrow disease. Due to the overall poor prognosis of MCL and its unique presentations, as demonstrated by our case, early detection and prompt treatment are crucial to survival.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and other hematologic malignancies. However, its use is associated with serious adverse effects including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can present with aphasia, mutism, somnolence, seizures, signs of increased intracranial pressure and rarely cerebral edema. Corticosteroids (CS) and IL-6 inhibitors are first line treatment for CRS and ICANS. Prolonged CS use has been associated with decreased over-all survival in CAR T-cell treated patients. Data on effective treatments for CART T-cell induced neurotoxicity is limited, especially in steroid-refractory ICANS. Blood-brain barrier (BBB) disruption and infiltration of myeloid and immune effector cells into the central nervous system are implicated in the pathogenesis of ICANS. This likely explains the role of intrathecal chemotherapy, which has been described in literature for treatment of steroid-refractory ICANS. Here, we report the outcomes of two patients with refractory DLBCL who developed severe ICANS after receiving axicabtagene ciloleucel (axi cel) and treated with intrathecal (IT) chemotherapy. Case Presentation Our first case is of a 66 year old male with diagnosis of R/R DLBCL, who was treated with R-CHOP, followed by R-GemOx, with no response then received axi cel. Patient developed grade 2 CRS and grade 1 ICANS (National Cancer Institute Common Terminology Criteria for Adverse Effects v4.03) on day +2 post infusion, treated with tocilizumab and dexamethasone with good response initially. While tapering dexamethasone on day +5, he developed grade 3 CRS and grade 3 ICANS. Brain MRI did not show any intracranial abnormality and EEG showed no seizure activity. Lumbar puncture (LP) was done on day +7 and showed opening pressure of 32 cm H2O, and 12 lymphocytes. He was started on IV solumedrol and tocilizumab was resumed. CRS improved while neurotoxicity progressed to grade 4 prompting intubation and mechanical ventilation on day +8. On day +9, patient received intrathecal methotrexate 12 mg and hydrocortisone 50 mg. On day +12, neurotoxicity improved to grade 1 and patient was extubated on day +13. Steroid taper stopped on +17. Despite disease response, patient remained hospitalized at day +45 for deconditioning and vocal cord paralysis related to a lengthy hospital stay and intubation. He was eventually discharged, however passed away on day +49 from complications of prolonged hospitalization. Our second case is of a 69 year old female with a diagnosis of R/R DLBCL with CNS involvement, treated with RCHOP x6 followed by salvage chemotherapy with refractory disease, She then received axi cel. Patient developed grade 1 CRS on day +4, treated with tocilizumab and dexamethasone, and patient responded well. On day +9, she developed grade 2 CRS and grade 3 ICANS. At that time, dexamethasone was switched to pulse dose solumedrol and tocilizumab was continued. CT head showed no acute intracranial abnormality and EEG did not show any epileptiform activity. LP showed opening pressure of 21, and 84 lymphocytes. On day +11, patient's CRS resolved, however ICANS developed to grade 4 and patient received 12 mg intrathecal methotrexate and hydrocortisone 50 mg for steroid-refractory ICANS. The very next day, patient showed significant neurological improvement. Steroid taper was initiated and patient's ICANS resolved on day +16. MRI brain showed decrease in size of nodular enhancement along periventricular white matter and left occipital area corresponding to treatment response. She was discharged on day +28 and continues to do well one year out of axi cel infusion Conclusion Our abstract adds to the sparse literature about the use IT chemotherapy in cases with severe ICANS. It also highlights its importance as an alternative potential therapy to high doses and prolonged courses of corticosteroids which is associated with increased morbidity and mortality. Steroid-refractory ICANS has limited treatment options and further evaluation of the use of IT chemotherapy in large scale studies is warranted. Disclosures Kahn: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genetech: Research Funding, Speakers Bureau; GSK: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Lister: Oncology Analytics: Other: Academic Board.

Introduction Determining eligibility for autologous hematopoietic stem cell transplantation (Auto-HCT) is considered standard of care for patients with newly diagnosed multiple myeloma (MM). In addition to comorbidity score, age >65 years is still a commonly used criterion to deem patients ineligible for transplant. Here we report the outcomes of patients ³ 65 years with MM who underwent Auto-HCT following risk stratification using HCT-CI along with other eligibility criteria. Methods We performed a retrospective analysis of 102 patients, who underwent Auto-HCT between 1/1/1999 and 12/31/2018 at Allegheny Health Network Cancer Institute. Ninety two patients (90%) received conditioning with Melphalan 200 mg/m2. Median overall survival (OS) was estimated at day+100, day+180, 1, 2, 3 and 5 years post Auto-HCT. Non-relapse mortality (NRM) was assessed at day 100 post Auto-HCT. Results For a cohort of 102 patients, a total of 119 Auto-HCT were performed. Median age at transplantation for the entire cohort was 69.2 years (65.1 - 79.4 years). Thirty five (34.3%) patients were aged ³70 years. Median HCT-CI score was 3 (range: 0-8). Median time to Auto-HCT following diagnosis was 9.1 months (range: 4.7- 176.7 months). Median time to ANC500 and PLT20 was 13 days (range: 10-15) and 18.4 days (range:8-42) respectively. Median OS by Kaplan-Meier analysis for the entire cohort vs patients ³ 70 years at day+100, day+180, 1, 2, 3, and 5 years post Auto-HCT was 97.1%, 95.1%, 91.2%, 83.3%, 78.4%, and 63.7% respectively vs 100%, 100%, 97.1%, 82.9%, 77.1% and 68.6% respectively. Median OS in months for patients Conclusion Auto-HCT in patients with MM aged ³65 years is safe, effective and should be offered to all patients with a reasonably good performance status. A fully integrated approach is required to accomplish the needs of elderly patients including consideration for quality of life.

Clostridium perfringes is a gram-positive, rod-shaped, anerobic, spore-forming pathogenic bacterium. C. perfringes is commonly known to cause tissue necrosis and gas gangrene. However, severe life-threatening complications like hemolysis due to clostridium sepsis are rarely encountered. We present a case of a 35-year-old female presenting with endometritis complicated with severe hemolysis in the setting of sepsis secondary to C. perfringes . Her hospital course was complicated with multi-organ involvement, requiring broad-spectrum intravenous antibiotics. Eventually, she made an uneventful recovery by early recognition of these rare complications and prompt institution of appropriate therapy. J Hematol. 2017;6(2-3):59-61 doi: https://doi.org/10.14740/jh328w

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is categorized as familial or acquired, most commonly caused by infections, malignancies, rheumatologic and immunodeficiency disorders. Irrespective of the etiology, the age at the onset is the strongest prognostic factor, hence it is extremely important to have a high suspicion for HLH, diagnose it promptly and initiate treatment without any delay. We encountered a 70-year-old female patient who initially presented with left-sided facial weakness and pancytopenia, secondary to diffuse stage IV B diffuse large B-cell lymphoma with isolated bone marrow involvement with secondary HLH. J Hematol. 2017;6(2-3):49-51 doi: https://doi.org/10.14740/jh324w

Introduction High-dose cytarabine (HD-AraC) is an important component of intensive post-remission therapy for acute myeloid leukemia (AML). Its efficacy in core-binding factor (CBF) AML has been well established but it remains controversial whether HD-AraC is effective before allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Herein, we report our experience at Allegheny Health Network (AHN) regarding the number of cycles of HD-AraC used before Allo-HSCT and its effect on survival. Methods We retrospectively analyzed 49 patients with AML who received HD-AraC after achieving complete remission and underwent Allo-HSCT at our institution between January 2010 and June 2018. Patients with acute promyelocytic leukemia (APL), CBF-AML, and primary induction failure were excluded. The HD-AraC dosing regimen used at our institution is 3,000 mg/m2 IV every 12 hours on days 1, 3, 5 for a total of 6 doses per 28-day cycle. Fifteen patients received 1 cycle, twenty patients received 2 cycles, and fourteen patients received >2 cycles of HD-AraC. The majority of the patients (n=32, 65%) received a myeloablative conditioning (MAC) regimen. The unadjusted probabilities of overall survival (OS) were estimated using Kaplan-Meier method and a multivariate analysis was performed using multiple logistic regression model for odds ratio, 95% confidence interval, and p-value. Number of HD-AraC cycles, age, conditioning regimen, and AML risk stratification per European Leukemia Net (ELN) were used as covariates. Results Median age was 56 years (IQR: 45.1-63.3) and median days to Allo-HSCT was 155 (IQR: 127-202). Our patients received a median of 2 cycles (IQR: 1-3) of HD-AraC before Allo-HSCT. With median follow up of 10 months, the median overall survival for patients who received 1, 2, and >2 cycles of HD-AraC was 9.9, not reached, and 33 months, respectively. Patients who received 2 cycles of HD-AraC showed a trend toward lower mortality with odds ratio of 0.22 (95% CI: 0.03-1.79, p-value 0.158). Conclusion Our data shows that patients who received two cycles of HD-AraC had a lower mortality rate with a trend towards significance. However, the majority of these patients also received a MAC regimen (n=18, 90%) which is significantly (p-value 0.005) more than patients who received 1 cycle (MAC n=6, 40%) and >2 cycles (MAC n=8, 57.1%) of HD-AraC. In addition to this bias that is related to the retrospective nature of the study, the small sample size as well as this being a single center experience limits definitive conclusions. Larger studies are needed to determine the optimal number of HD-AraC as a bridge to Allo-HSCT.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder, described as a clinical triad of microthrombocytopenia, eczema and recurrent infections. Different mutations in WAS gene have been identified, resulting in various phenotypes and a broad range of disease severity, ranging from classic WAS to X-linked thrombocytopenia and X-linked neutropenia. WAS in some cases can be fatal without haematopoietic stem cell transplantation early in life. In this particular case, we present a novel mutation with a unique presentation. An 18-year-old man incidentally found to have macrothrombocytopenia and neutropenia at 16 years of age later found to be hemizygous for c. 869T>C (p.Ile290Thr) mutation in WAS gene. The late presentation, absence of other manifestations of WAS and presence of macrothrombocytopenia, rather than microthrombocytopenia, which is usually a characteristic finding in WAS, misled the initial diagnosis. On review of literature, this mutation has not been reported as causing WAS.

BackgroundPropylthiouracil has been in use for more than half a century for the treatment of hyperthyroidism. While it is largely known to cause agranulocytosis, its association with aplastic anemia is rarely heard of. Our case will be the third in literature to suggest aplastic anemia as a manifestation of propylthiouracil, which unfortunately culminated in the death of the patient.CaseA 67-year-old female, with recently diagnosed metastatic adenocarcinoma of the lung, developed hyperthyroidism after being started on Nivolumab and Iplimumab. After she developed atrial fibrillation, she was started on propylthiouracil to control the thyroid activity. Soon after that, she was admitted with severe neutropenia, which progressed to pancytopenia confirmed as aplastic anemia on a bone marrow biopsy. Despite discontinuation of propylthiouracil and aggressive treatment, she developed septic shock and multi-organ failure, leading to her death.ConclusionAplastic anemia has been sparingly reported as an extremely rare complication of propylthiouracil. Further adding to the ambiguity is the unknown etiology and lack of specific therapy for the complication when attributed to propylthiouracil. The disease can carry an extremely poor prognosis if untreated, as proven by our case. Due to the same reasons, we recommend that further investigations be done to elucidate the pathogenesis and assist with treatment of the disease when caused by propylthiouracil.

Introduction BK virus hemorrhagic cystitis is a well-recognized complication in patients undergoing allogeneic HSCT and is associated with significant morbidity. PTCY has been used for GVHD prophylaxis in patients undergoing haploidentical or mismatched unrelated donor HSCT. We hypothesized that PTCY is associated with increased incidence of HC associated with BK virus. Objectives • To identify the risk factors for developing BKHC in allogeneic HSCT • To assess the effect of PTCY in development of BKHC in patients with myeloablative (MA) regimen containing total body irradiation (TBI) • To evaluate the risk of concurrent CMV infection and BKHC in allogeneic HSCT with MA conditioning regimen Methods We identified 116 consecutive patients who underwent allogeneic HSCT at our institution between January 2015 and July 2018. The MA regimen (n=42) consisted of fludarabine 50 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 4 days with or without TBI of 200 cGy/day for 2 days (FBT or FB4). The reduced intensity conditioning (RIC) regimen (n=74) consisted of fludarabine 30 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 2 days (FB2). In terms of GVHD prophylaxis all recipients except those undergoing haploidentical and mismatched unrelated transplant received Thymoglobulin 2 mg/kg/daily IV days -2, -1 and 0 (n=80). Recipients of haplo- related and mismatched unrelated donor transplantation received cyclophosphamide 50 mg/kg IV on day +3 and +4 along with Mesna (n=36). All patients received post-transplant immunosuppression with Tacrolimus and Mycophenolate Mofetil. Patients with urinary symptoms were tested for BKV in urine by PCR. Results The median age of patients was 56 years (range 20–76). A total of 31% of patients (n=13) received PTCY in FBT group which was similar to 31% of patients (n=23) in FB4-FB2 (p=0.98). Overall 21.5% patients were diagnosed with BKHC. The patients who received ATG, the incidence of BKHC was 27.5% in FBT group and 11.7 % in FB4-FB2 (p=0.073). The patients who received PTCY, the incidence of BKHC was significantly increased to 69.2% in FBT vs 9% in FB4-FB2 (p=0.0001). The risk of developing concurrent CMV viremia and BKHC was increased to 10.3% in FBT compared to 5.8% in FB2-FB4 (p=0.662). The patients who received PTCY following FBT, the incidence of concurrent CMV viremia and BKHC was increased to 23.1%. as compared to 0% with FB2-FB4. Conclusion Our result shows the addition of PTCY to TBI containing regimen significantly increased the incidence of BKHC. We did not observe increase in the incidence of BKHC in patients receiving PTCY with FB2 or FB4 regimens. Our study revealed an increased incidence of concurrent BKHC and CMV viremia in patients receiving PTCY with FBT which could be due to increased immunosuppression. Our findings suggest that using PTCY as GVHD prophylaxis in patients undergoing MA conditioning regimen including TBI is a risk factor for BKHC.

Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.

Correction to: memo 2019 https://doi.org/10.1007/s12254-019-0487-4 The original version of this article unfortunately contained a mistake. The spelling of the last author’s name is “Prerna Mewawalla”. The original article has been …

Introduction Disease Status of AML patients at the time of HSCT is an important factor in predicting their survival. We hypothesize that MLFS (as per IWG criteria) identifies a group of patients that have better outcome than PIF (as per CIBMTR criteria). Objectives • To identify group of patients previously categorized as PIF by CIBMTR pretransplant that may have favorable outcome with HSCT. • To assess the outcome of patients with primary refractory disease by IWG criteria with HSCT. Methods We retrospectively analyzed 78 patients with AML who underwent allogeneic HSCT between June 2008 and December 2017 at our institution. We assessed the disease status at time of transplant as per CIBMTR criteria as complete remission (CR) defined as 1000, platelets >100,000 with transfusion independence, and primary induction failure (PIF) defined as not achieved CR or CRi. We also assessed the patients at time of transplant as per IWG criteria as CR (similar to CR as per CIBMTR but does not require normal maturation), morphologic leukemic-free state (MLFS) defined as 5%. We compared the OS at one year for the above groups. The patients received myeloablative conditioning with FBT or reduced intensity conditioning with FB2. Results Per IWG criteria, The OS at 1 year was 62 % in the CR group (n=29), 65% in the MLFS group (n=17) and 22% in the PRD group (n= 32). Our analysis revealed an overall statistically significant difference between CR v PRD, p=0.0009 and MLFS v PRD, p=0.0006. When we used the CIBMTR criteria, both MLFS and PRD were reclassified into the PIF group with OS of 34% (n=49). Conclusion Disease status prior to transplant is a predictor of outcome after allogeneic HSCT. Our analysis shows better survival for patients who achieved MLFS prior to transplant according to IWG criteria as compared to patients who were classified as primary induction failure by CIBMTR criteria. We intend to prospectively use the IWG criteria pre-transplant in our patients to help predict their survival at one year.

Introduction and Objectives Multiple myeloma (MM) is a disease of the elderly with the median age of diagnosis being 66 years and rare in the population younger than 50 years. Younger patients generally undergo autologous HCT as part of their treatment once they achieve an adequate response. Overall survival in patients with MM has dramatically improved over the last 2 decades with the advent of novel agents. The purpose of this retrospective analysis was to evaluate the disease behavior and transplant outcomes in patients younger than 50 years. Methods We retrospectively reviewed the charts of 29 patients aged ≤50 who underwent autologous HCT between May 2003 and Dec 2017 at our institution. All patients received Melphalan as their conditioning regimen. 28% (n=8) of the patients had renal insufficiency at the time of diagnosis (serum Creatinine ≥ 2.0 mg/dl). Results 38 auto-HCTs were performed in this group of patients. 7 patients underwent salvage transplant and 2 patients underwent planned tandem auto-HCT. Nearly 80% (n=23) patients had Salmon Durie stage 3 disease at the time of auto-HCT. Overall survival for the entire cohort was 109 months and PFS was 51 months. Median age at diagnosis was 46 years. The median age of the first transplant is 47 years. Median time to relapse/progression was 31 months after auto-HCT for the entire cohort. For patients with high-risk cytogenetics (28%, n=8) median time to relapse was 13 months compared to 72 months in standard risk patients. There was total of 12 deaths in the entire cohort with the majority of deaths (10/12) due to disease progression/relapse and 1 died from a secondary malignancy. Median time to relapse/progression after salvage HCT was 16 months. Of the 7 patients who underwent salvage HCT, 3 died secondary to disease progression with a median time to death is 12.6 months. Conclusion Despite recent advances in the treatment of multiple myeloma, younger patients with high-risk disease status continue to have poor outcomes. Aggressive induction regimens and possible planned tandem Auto-PBSCT may be a reasonable approach to improve outcomes in younger patients with high-risk disease status. Further studies with a larger cohort are warranted to corroborate our findings and also find ways to improve survival in this high-risk group.

Human immunodeficiency virus infection has been implicated in multiple viral-based processes adversely affecting the renal system, including HIV-associated nephropathy (HIVAN), HIV-related immune complex disease, and the less well-described HIV-related thrombotic microangiopathy (TMA). While HIV nephropathy has an overall poor renal prognosis and is treated primarily with anti-viral therapy, the etiology of HIV-related (non-thrombotic thrombocytopenic purpura-associated) renal TMA may be causally linked to viral amplification of a dysregulated alternate complement cascade. Thus, if detected in its incipient stages, the associated renal injury may respond similarly to complement-inhibitory modalities as has been observed in cases of non-virally-linked TMA (aHUS), thus yielding significant recovery of kidney function. We report a case of a 43-year-old male patient with a history of advanced HIV disease and chronic renal insufficiency, previously attributed to HIVAN, who presented with acute renal decline, microangiopathic hemolytic anemia and thrombocytopenia, and biopsy-proven renal TMA, whose acute renal decompensation responded favorably to terminal complement blockade (eculizumab). J Hematol. 2015;4(1):141-143 doi: http://dx.doi.org/10.14740/jh183w

Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease.Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase.Five centers from India with experience in treating lysosomal storage disorders.The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for6 months. Indications for treatment included symptomatic anemia, thrombo-cytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days.Hemoglobin, platelet counts, liver and spleen volumes and growth parameters.22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 10(9)/L (-98.5 x 109 to 145.5 x10(9))/L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static.This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.

e20015Background: The prevalence of multiple myeloma (MM) in the US has increased from 50,484 cases in 2002 to 118,539 cases in 2014 per the SEER database. Overall survival has improved with the ad...

e19010Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APML). Anthracycline is added at induction for high ri...

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of dysregulated immune activity with macrophage activation that can manifest as pancytopenia, coagulopathy and other laboratory abnormalities, usually progressing to multiorgan failure and death. This report documents the rarely reported association between HLH and Hodgkin’s lymphoma (HL) with simultaneous HIV and Epstein-Barr virus (EBV) and complete resolution with chemotherapy. The patient initially presented with cholestatic jaundice. He was then found to have HL associated with HLH with coexistent HIV and EBV viraemia. A-Brentuximab-VD regimen for the lymphoma was initiated, resulting in rapid resolution of HLH and ultimately remission of HL. HLH is a syndrome known to have high mortality; thus, early diagnosis and prompt treatment are crucial. Usual presentation includes non-specific symptoms and can easily be overlooked. This case highlights the importance of diagnosing the condition in unusual settings and attempting treatment by targeting the cause of HLH, HL in our case.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia and is characterized by a highly variable clinical course. In the past decade, several prognostic risk factors have been identified facilitating the classification of CLL into various risk groups. Patients with poor risk disease, such as poor cytogenetics or relapsing after purine-based analogues, had limited therapeutic options, with allogeneic hematopoietic cell transplantation (allo-SCT) the only known therapy with curative potential. More recently, the introduction of novel agents inhibiting the B-cell receptor pathway, and the early success with chimeric antigen receptor T cells offers an effective and relatively safe option for this poor prognostic group which holds promise in the future. Alternatively, the use of reduced intensity conditioning regimens in the allo-SCT setting has led to a significant decrease in nonrelapse mortality to 16–23%, making it an attractive therapeutic option. No recent guidelines have been developed since these novel therapies became available regarding the optimal time to allo-SCT in this patient population. The advent of these novel and highly active therapeutic agents, therefore, warrants a reappraisal of the role and timing of allo-SCT in patients with CLL. In this article, we summarize the literature regarding the novel therapeutic agents available today as well as focus on the efficacy and safety of allo-SCT.

Background: There have been significant improvements in the outcomes for patients with multiple myeloma over the past 10 years. The course of the disease remains highly variable. While some patients experience 10-15 year survivals, others succumb to highly refractory disease within a few months. Many studies have focused on the description of prognostic factors capable of predicting this heterogeneity in survival. Baseline Serum free light chain concentration is a major prognostic indicator for plasma cell neoplasms and normalization of free light chain ratio with treatment has been reported as an indicator for favorable prognosis. High Baseline free light chain concentration at presentation indicates aggressive disease. Furthermore High serum free light chain ratio correlates with elevated serum creatinine, elevated LDH and extensive marrow infiltration. Objectives: To determine if serum free light chain concentration > 1000mg/dl at the time of diagnosis and at disease progression was an independent prognostic marker for multiple myeloma. Methods: The results of all the serum free light chain analyses of patients evaluated at western Pennsylvania hospital between 2007 -2015 were reviewed and patients with serum free light chain concentration >1000mg/dl at the time of initial diagnosis and disease progression were identified Retrospective chart review was done to study the survival in these patients. Results: Total of 15 patients in whom serum free light chain concentration was greater than 1000 mg/dl at diagnosis were identified. Median age at diagnosis was 60.81 years (45.2-77.3). The median survival in this population is 1.85 years (range 0.06-8.85 years), with 5 deaths. Of these 15, 9 patients received an autologous PBSCT as a part of their initial therapy. Six of them are alive with a median overall survival of 2.44 years and mean survival of 3.89 years (range 0.87-8.89). In the remaining 6 patients that did not undergo an auto PBSCT 3 of them are alive with median overall survival of 1.21 years and a mean survival 1.20 years (range 06-2.76 years). There is an overall trend toward very poor prognosis in this specific group of patients irrespective of the age, sex, stage at time of diagnosis, the immunoglobulin subtype and the free light chain subtype (kappa vs lambda). We also conducted a retrospective review of patients in whom serum free light chains concentration was greater than 1000mg/dl at disease progression. Twenty patients were identified all of whom are deceased with a median overall survival from the time of progression with serum free light chains greater than 1000 mg /dl was dismal at 0.27 years and mean survival was 0.53 years (range 0.04-2.52 years) Conclusion: Patients with multiple myeloma who presented with a serum free light chain concentration greater than 1000 mg/dl at diagnosis have very poor prognosis. These specific subgroups of patients should be identified and treated aggressively at the time of diagnosis to prevent complications from multiple myeloma and improve their overall survival. In our small cohort of patients those who underwent auto PBSCT as a part of their initial therapy tend to have better outcomes in terms of overall survival compared to patients who received therapy without auto PBSCT consolidation. Patients with serum free light chains greater than 1000 mg/dl at disease progression will need to be treated aggressively with perhaps a salvage auto PBSCT to improve their overall outcome. A larger study to evaluate elevated serum free light chains (greater than 1000 mg/dl) as a prognostic indicator at diagnosis and progression should be done to further validate these findings Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

8064Background: There have been significant improvements in the outcomes for multiple myeloma patients over the past 10 years. However, the prognosis of the disease remains highly variable. While s...

The high risk of another cancer once one has been diagnosed is well known. Furthermore, a clear association exists between the use of some cytotoxic agents and chemotherapy-induced malignancies.This review is set to explore the relationship between multiple myeloma, its modern therapies and the development of second cancers due to various genetic, immune, and environmental (including iatrogenic) factors. Most relevant publications were identified through the PubMed database and by reviewing the drug information released by the US Federal Drug Administration.Our comprehensive analysis identified several retrospective population studies, cohort group analyses and a number of case reports linking myeloma with other cancers in the world literature. A majority of these studies suggest that incidence of second solid and hematologic malignancies is significantly increased in patients with multiple myeloma and its precursor lesion, monoclonal gammopathy of unknown significance. In addition, incidence of second malignancies has been found increased in the family members of these individuals, especially in their first-degree relatives.Analysis of the existing literature cohorts does not discriminate between the burden of second cancers in treated myeloma patients as opposed to the patients followed with the wait-and-watch approach. Notably, the rate of second malignant neoplasms in multiple myeloma may be further increased by certain myeloma therapies. These cancers include, for the most part, hematologic malignancies such as acute leukemias and certain lymphomas. While there is no question about the role of alkylating agents and topoisomerase II inhibitors in this regard, further research is necessary to determine whether the excess of second cancers represents a direct consequence of lenalidomide use.

Current literature suggests a variety of immune abnormalities are present in myelodysplastic syndrome (MDS) patients. However, they have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. In addition, an increased incidence of various autoimmune conditions has been documented in MDS patients.The authors offer a comprehensive review of the existing literature on immune mechanisms involved in the pathogenesis of MDS, various immune abnormalities documented in its course, their link with the clonal evolution of MDS as well as immune alterations induced by the existing MDS therapies.The course of MDS is accompanied by complex immune alterations, including T-cell and NK-cell defects, decreased functional abilities of neutrophils and antigen-presenting cells, altered antibody and cytokine production. While contemporary MDS therapies are shown to possess some immunomodulatory properties, authentic autoimmune conditions have also been documented with lenalidomide and recombinant erythropoietin. Caution should be exerted with the use of these agents in MDS patients with evidence of autoimmune disorders, as exacerbation of autoimmune phenomena can be anticipated. While the heterogeneity of MDS represents an inherent limitation, integration of emerging information from molecular biology, genetics, immunology research and clinical practice could translate into improved outcomes of this disease spectrum.

e18543 Background: Recent literature suggests that an association exists between marginal zone lymphoma (MZL) and certain autoimmune conditions. Furthermore, MZL and autoimmune diseases may share same pathogenesis in these patients. The present study was set to identify the prevalence of autoimmune phenomena in MZL patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=24) with MZL that had been followed in outpatient setting. Median age was 71.8 years (range, 50-96). Records were reviewed for the presence of autoimmune abnormalities; length of the prospective analysis segment was ~24 months. Prevalence of autoimmune disorders in our cohort was compared to their respective prevalence in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p-value < 0.05 was considered significant. Results: A total of 50% patients included in our study had documented autoimmune conditions. Identified autoimmune disorders included Hashimoto thyroiditis (n=5), immune thrombocytopenia [ITP] (n=4), rheumatoid arthritis [RA] (n=1), Raynaud's phenomena (n=1), psoriasis (n=1), and autoimmune hemolytic anemia [AIHA] (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.037), ITP (p

6555 Background: Review of literature suggests certain autoimmune abnormalities to accompany LGL leukemia. The present study was set to identify the prevalence of autoimmune phenomena in LGL leukemia patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=11) with LGL leukemia that had been followed in outpatient setting. Median age was 71 years ( ± 14 years). The presence of associated autoimmune disorders in our cohort was compared to the published prevalence of these conditions in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p value < 0.05 was considered significant. Results: A total of 45% patients in our study were diagnosed with autoimmune conditions. Identified autoimmune disorders included rheumatoid arthritis [RA] (n=3), Hashimoto thyroiditis (n=3), Felty syndrome (n=1), aplastic anemia (n=1), pernicious anemia (n=1), and leukocytoclastic vasculitis (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.044), RA (p=0.003), Felty syndrome (p