Smith Giri

Impact of hospital volume on outcomes of patients undergoing chemotherapy for acute myeloid leukemia: a matched cohort study

To the editor: In recent years, there has been growing evidence that hospital volume affects survival among patients undergoing a variety of surgical procedures and medical treatments.[1][1],[2][2] Whether case volume affects outcomes after chemotherapy among patients with acute myeloid leukemia (

Rituximab-induced serum sickness: A systematic review

OBJECTIVES To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. METHODS A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0. RESULTS In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögrens syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d. CONCLUSION It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.

Eculizumab in Transplant-Associated Thrombotic Microangiopathy.

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. Methods: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. Results: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. Conclusion: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.

Left Atrial Appendage Aneurysm: A Systematic Review of 82 Cases

Aneurysm of the left atrial appendage is rare. We sought to systematically review the published literature on left atrial appendage aneurysm (LAAA) to address its demographic features, clinical characteristics, treatment, complications, and outcomes.

Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis

Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs. 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs. 11 months), 1 year OS: 35% vs. 47% (p=0.05), 2 year OS: 16% vs. 31% (p<0.01), and 5 year OS: 7% vs. 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.

Right atrial appendage aneurysm: a systematic review.

Right atrial appendage aneurysm (RAAA) is rare with fewer than 20 cases reported in the literature. We sought to systematically review the published cases of RAAA in terms of demographics, clinical characteristics, treatment, complications, and outcome.

Central Nervous System Complications and Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation

BACKGROUND Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. PATIENTS AND METHODS This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. RESULTS Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). CONCLUSION The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes.

Ibrutinib has some activity in Richter’s syndrome

Richters syndrome (RS), defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, is seen in about 2–10% of all CLL patients. The prognosis of RS is extremely poor with a median survival of about 6 months, although patients with clonally unrelated RS may have a better prognosis. No randomized controlled trials exist to date regarding therapeutic strategies in these patients. Data from phase I/II single-arm studies testing various therapeutic strategies have shown limited survival benefit with significant toxicity. Here, we present two cases of RS treated with a novel therapeutic agent, ibrutinib (Table 1). Patient A was a 60-year-old male diagnosed with Rai stage IV CLL after evaluation of progressive lymphadenopathy. Fluorescence in situ hybridization (FISH) showed no deletion of ataxia telangiectasia mutated gene, chromosome 11q (ATM), chromosome 13q14.3, or p53. One month later, he developed rapidly progressive lymphadenopathy that upon biopsy revealed clonally related, activated B-cell type (ABC) diffuse large B-cell lymphoma (DLBCL) with a proliferating index Ki-67 of 50% consistent with RS. He was treated with cycles of rituximab/cyclophosphamide/ doxorubicin/vincristine/prednisone (R-CHOP), rituximab/ifosfamide/ carboplatin/etoposide (RICE) and rituximab/gemcitabine/oxaliplatin; however, his disease was refractory to these conventional therapeutic regimens. He was not a candidate for allogeneic hematopoietic stem cell transplantation due to a lack of insurance. Thus, the patient was started on ibrutinib. One month later, computed tomography (CT) scan revealed 70% regression of his disease, which improved at 3 months to 90% regression of disease. Patient B was a 59-year-old male who was diagnosed with Rai stage III CLL after evaluation of anemia with lymphocytosis. He was observed for 8 years until he developed progressive lymphocytosis that required treatment of his CLL with bendamustine/rituximab and fludarabine/cyclophosphamide/rituximab. FISH showed trisomy 12 in 34% of nuclei and deletion of p53 in 40% of nuclei, but deletion of ATM and 13q14.3 were not detected. Subsequently, he developed fever, night sweats and rapidly progressing lymphadenopathy for which biopsy of his right neck lymphadenopathy revealed clonally related, ABC DLBCL with a proliferating index Ki-67 of 90% consistent with RS. He was treated with multiple cycles of R-CHOP and RICE. He had poor prognostic features, given his p53 deletion, high LDH level and bulky disease with lung nodular disease. His lymphoma was refractory to these conventional therapeutic regimens, and he was not a candidate for allogeneic hematopoietic stem cell transplantation due to a lack of insurance. Thus, he was started on ibrutinib. CT scan 2 months later showed 100% progression of his neck adenopathy. Ibrutinib was stopped after 3 months due to refractory disease. Recent studies have shown that ibrutininb, a potent inhibitor of Brutons tyrosine kinase receptor, is a viable therapeutic option in cases of relapsed/refactory CLL. It remains unclear if this drug is effective against patients with RS as well. In an earlier phase Ib/II study on combination of ibrutinib with ofatumumab, a partial response was seen in two out of three patients with RS. It was not clear that whether these patients had different genetic profiles. In our case, both patients had ABC type DLBCL, which has been shown to have a better response to ibrutinib as compared with germinal center B-cell type DLBCL. However, patient A had an excellent response whereas patient B was refractory to ibrutinib therapy. In contrast to patient A, patient B had high-risk mutations (deletion of p53 and trisomy of chromosome 12) and a highproliferation index (Ki-67 of 90%) suggesting a poor prognosis. This may suggest that ibrutinib is beneficial in a select group of patients with distinct genetic profiles. Our experience with these patients adds to a growing hypothesis that ibrutinib may be a viable therapeutic option in CLL patients with RS.

Novel mutations in a patient with ALK-rearranged lung cancer.

A variety of mechanisms of crizotinib resistance have been defined in patients with ALK-rearranged lung cancer who no longer have a response to the drug. A case is presented in which the tumor lost the rearrangement and mutations developed in several other genes.

Early mortality in acute myeloid leukemia

The Southwest Oncology Group (SWOG) described the expected early mortality rate (EMR) for patients with non-M3 AML by age enrolled in clinical trials, but it is unclear how generalizable this data is. We sought to compare SWOGs reported EMR to that of the general population by utilizing the case listing session of SEER 18 matched to the accrual periods of the SWOG studies. 26,272 patients were identified within SEER compared to 968 in the SWOG cohort with mortality data. The EMR was 26.7% (7022 events) in the SEER cohort versus 12.2% (116) in the SWOG cohort. The EMR was higher in the SEER cohort in every studied age group and definition of EMR. Stepwise logistic regression analysis identified increasing age, black race (OR 1.15, CI 1.03-1.29, p<0.01), and monocytic differentiation (OR 1.55, CI 1.27-1.89, p<0.01) as predictors of higher EMR. This study demonstrates that EMR in patients with non-M3 AML is higher in the general patient population than reported in SWOG clinical trials.