Binay Kumar Shah

HIV-associated primary bone marrow Hodgkin's lymphoma: a distinct entity?

Primary bone marrow Hodgkin’s lymphoma (PBMHL) in patients with HIV is rare with few patient case reports. We describe a patient with HIV-associated PBMHL who presented with fever and cytopenias. We reviewed the literature and present clinical characteristics of HIV-associated PBMHL. A 43-year-old African American man with history of HIV/AIDS was admitted with a recurrent fever, night sweats, and malaise of several weeks in duration. The patient denied any change in appetite or weight loss. He denied any history of smoking, alcohol abuse, or illicit drug use. His home medications were antiretroviral medication and trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis. There was no family history of blood dyscrasias or malignancies. Physical examination did not reveal any lymphadenopathy or hepatosplenomegaly. Laboratory results revealed pancytopenia with WBC of 2,100/ L, hemoglobin of 9 g/dL, and platelet count of 115,000/ L. The absolute neutrophil count was 1,700/ L. An infection work-up was negative. The patient underwent bone marrow aspiration and biopsy for evaluation of cytopenias. Bone marrow biopsy showed hypercellular marrow with present but decreased hematopoiesis as a result of a dense infiltrate of large atypical cells with bilobed nuclei, prominent eosinophilic nucleoli, and abundant cytoplasm typical of Reed-Sternberg cells (Fig 1) as well as many variants. The background consisted of abundant lymphocytes, plasma cells, histiocytes, and eosinophils. Immunohistochemical stains showed that the large, atypical Reed-Sternberg cells were positive for CD15 and CD30 and negative for CD2, CD3, and CD20 antigens. Diagnosis of Hodgkin’s lymphoma (HL) was made based on the characteristic morphology and immunophenotype. Staging computed tomography scans of the neck, chest, abdomen, and pelvis were negative for lymphadenopathy or hepatosplenomegaly. The patient had a normal ejection fraction on multiple-gated acquisition scan and normal pulmonary function tests. The lymphoma was determined to be stage IVB per Ann Arbor staging system, based on the findings of bone marrow involvement and “B” symptoms. A decision was made to treat the patient with doxorubicin, bleomycin, vinblastine, and dacarbazine for six to eight cycles. The patient has completed two cycles of therapy and is doing well. HL is five to 10 times more common in patients with HIV infection. HIV-associated HL is usually widespread at presentation Fig 1.

Disparities in chronic myeloid leukemia survival by age, gender, and ethnicity in pre- and post-imatinib eras in the US.

Abstract Background. Since May 2001, imatinib mesylate has become the first-line therapy for chronic myeloid leukemia (CML) but the survival pattern by age, sex, and ethnicity is not clear. Material and methods. We analyzed the Surveillance, Epidemiology, and End Results (SEER*Stat) database to compare survival rates in CML among Caucasians, African-Americans (AA), and other races, and also within each race to see survival differences from the pre-imatinib (1973–2000) to post-imatinib eras (2002–2008). We used Z-tests in SEER*Stat to compare relative survival rates categorized by race, gender, and age groups (all ages, < 50, 50+ years). Results. The three-year relative survival rates among Caucasians, AA, and other races in the pre-imatinib era were 44.9 ± 0.6%, 46.8 ± 1.8%, and 48.0 ± 2.2%, respectively, and in the post-imatinib era 64.4 ± 0.8%, 67.3 ± 2.4%, and 69.6 ± 1.6%, respectively. The relative survival increased from the pre-to post-imatinib era for all ethnic groups. In the post-imatinib era, three-year relative survival rates among young AA women were significantly lower (Z-value = −2.54, p = 0.011) than young Caucasian women, 80.5 ± 4.5% (n = 105) vs. 90.3 ± 1.4% (n = 589). Conclusions. The relative survival rates of CML patients have improved in the post-imatinib era. However, the improvement in survival rates has been modest in this population-based data compared to those reported from randomized trials. Improvement in survival among older patients is lower than in younger patients. Young (<50 years) AA women with CML had lower relative survival rates compared to young Caucasian women in the post-imatinib era.

Improved survival among older acute myeloid leukemia patients – a population-based study

Abstract Background. Survival in acute myeloid leukemia (AML) has improved in younger patients over the last decade. This study was conducted to evaluate the relative survival rates in older AML patients over two decades in the US. Material and methods. We analyzed Surveillance, Epidemiology, and End Results (SEER) registry database to evaluate relative survival rate in older (≥ 75 years) AML population diagnosed during 1992–2009. We selected AML patients from 13 registries of SEER 18 database to compare RS during 1992–2000 and 2001–2009. Results. The relative survival rates improved significantly during 2001–2009 compared to 1992–2000 for all age groups and sex. For young elderly patients (75–84 years) RS increased from 13.1 ± 0.8% to 17.4 ± 0.9% at one year Z-value = 3.98, p < 0.0001 and from 2.0 ± 0.4 to 2.6 ± 0.5%, Z-value = 3.61, p < 0.0005 at five years. Similarly, for very elderly (≥ 85 years) patients RS increased from 5.3 ± 1.0% to 8.0 ± 1.0%, Z-value = 3.03, p < 0.005 at one year, but no improvement seen at five years. Conclusion. The relative survival in elderly AML has increased significantly during 2001–2009 compared to 1992–2000.

Rituximab‐induced acute severe thrombocytopenia

A 73-year-old woman with a past medical history of hypertension was evaluated haematologically because of lymphocytosis found on a routine blood count. Her only complaint was of progressive fatigue for a few months. Physical examination showed pallor, right posterior cervical lymphadenopathy and moderate splenomegaly. A full blood count showed a white cell count of 18AE2 · 10/l with 82% lymphocytes and a normocytic normochromic anaemia with haemoglobin concentration of 100 g/l. A computed tomography scan of the abdomen showed an enlarged spleen (25 cm). Bone marrow biopsy showed mantle cell lymphoma. The patient was treated with a modified Hyper-CVAD-R (cyclophosphamide, vincristine, doxorubicin, dexamethasone, rituximab) regimen. She developed chills without fever or hypotension during the rituximab infusion on day 1 of cycle 1. Her platelet count dropped from a preinfusion level of 85 · 10/l to 14 · 10/l the next day but there were no signs of bleeding. Three days later, her platelet count had increased to 118 · 10/l. She did not require platelet transfusion and was discharged home in good condition. She developed acute severe thrombocytopenia following each dose of rituximab during subsequent cycles of chemotherapy (Figure). The thrombocytopenia improved spontaneously over 2–3 d on each occasion.

Idelalisib- a PI3Kδ targeting agent for B-cell malignancies

Idelalisib, the first in-class phosphotidlyinositol 3-kinase delta (PI3Kδ) inhibitor, was approved by the US Food and Drug Administration in July 2014. It simultaneously received breakthrough therapy designation in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia (CLL) as well as accelerated approval as monotherapy for the treatment of relapsed follicular lymphoma and relapsed small lymphocytic lymphoma. In a pivotal phase III study of 220 patients with relapsed CLL, the overall response rate of patients who received rituximab plus idelalisib was 81%. The median progression-free survival (PFS) was 5 months with rituximab plus placebo group, but was not reached in the idelalisib arm. At 24 weeks, the PFS in patients receiving idelalisib was 93%. In a phase II trial of 125 patients with relapsed or refractory indolent non-Hodgkin lymphoma who received idelalisib 150 mg twice daily, the response rate was 57%. Complete response was seen in 6% of patients. The median duration of response was 12.5 months, and median PFS was 11 months. Idelalisib is a promising new therapy for relapsed indolent B-cell malignancies.

Survival trends among patients with advanced renal cell carcinoma in the United States.

Introduction: Since the approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into a survival benefit in a population-based cohort. Methods: We analyzed the SEER 18 (Surveillance, Epidemiology and End Results) registry database to calculate the relative survival rates for advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009. We also evaluated the survival rates by age (<65 and ≥65 years) and sex. Results: The total number of advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009 were 7,047, 4,059, 1,548 and 1,440, respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7 ± 0.6 and 10.0 ± 0.4%, respectively. There was no significant difference in 1-year relative survival rates for patients diagnosed during 2006-2007 and 2008-2009 compared to those diagnosed during 2001-2005. Similarly, the 3-year survival rates for patients diagnosed during 2006-2007 were similar to those diagnosed during 2001-2005. Conclusions: This population-based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents.

Pemetrexed-induced anaphylaxis

Pemetrexed is a folate antimetabolite approved for the treatment of mesothelioma and locally advanced or metastatic non-squamous non-small cell lung cancer [1]. It is generally well-tolerated, with myelosuppression as the most common dose-limiting toxicity. Rare serious side effects of anticancer drugs may be identifi ed during postmarketing experience. We report the fi rst case of pemetrexedinduced anaphylaxis. A 53-year-old female with metastatic adenocarcinoma of the lung on chemotherapy with intravenous pemetrexed 500 mg/m 2 followed by cisplatin 75 mg/m 2 every three weeks presented to the offi ce for her sixth cycle of treatment. Besides mild fatigue, patient denied any symptoms. Her home medications included folic acid 1 mg po daily. She was on intramuscular cyanocobalamin 1000 μ g every nine weeks. Her baseline vitals showed temperature 99°F, pulse 99/minute, respiratory rate 16/ minute, blood pressure 111/75 mm Hg, and O 2 saturation 95% on room air. Blood work showed WBC 4400/μl with 40.3% granulocytes, hemoglobin 13.3 g/dl, and platelet count 191,000/μl. Liver and kidney function were within normal limits. Prior to chemotherapy, the patient received premedication with dexamethasone, ondansetron, and fosaprepitant. Seven minutes into the pemetrexed infusion, the patient suddenly developed nausea, shortness of breath, audible wheezing and fl ushing. Her blood pressure increased to 149/90 mm Hg, and her heart rate increased to 134/minute, with a respiratory rate of 32/minute. Her O 2 saturation decreased to 88% on room air. The chemotherapy was discontinued. Bolus IV normal saline and oxygen were administered, along with 50 mg diphenhydramine IV followed by 20 mg dexamethasone IV. Over the course of the next hour, the patient ’ s symptoms gradually resolved and she was discharged in a stable condition. Discussion

Disparities in Receipt of Radiotherapy and Survival by Age, Sex, and Ethnicity among Patient with Stage I Follicular Lymphoma.

Background Radiotherapy (RT) is a first-line treatment option for stage I follicular lymphoma (FL). We studied disparities in receipt of RT and survival among patients with stage I FL. Methods Adult patients (age ≥18 years) with stage I FL, as the first primary cancer, diagnosed between 1992 and 2007 were identified using Surveillance, Epidemiology, and End Results (SEER) 18 database. Study population was divided into various subgroups based on age, sex, race, and marital status. Factors associated with receipt of RT and survival, among patients receiving RT, was evaluated using regression analysis and Cox PH modeling, respectively. SEER*Stat was used to compute 1- and 5-year RS for various subgroups and compared using Z score. Results Of the total 7315 patients (median age: 64 years), 2671 (36.5%) received RT. African-Americans, older age group, and single and separated/divorced/widow marital status predicted omission of RT. The 1- and 5-year RS were significantly better in patients receiving RT. In multivariate analysis, male sex, age <60 years, Caucasian race, and married marital status were found to be independent predictor of better RS among patients receiving RT (P < 0.0001). Conclusion This study showed that 36.5% patients with stage I FL received RT. Survival rates were significantly better for patients who received RT.

Second Primary Malignancies in Adults with Gastric Cancer - A US Population-Based Study.

Background Multiple studies have examined the incidence of secondary primary malignancies (SPMs) in gastric cancer patients in Europe and Asia. This retrospective review was conducted to analyze risk of SPM in patients with gastric cancer diagnosed in the United States. Methods We included adult patients diagnosed with gastric cancer from the surveillance, epidemiology, and end result (SEER) 13 database. We calculated the risk of SPMs in these patients using the multiple primary standardized incidence ratio session of SEER*stat software and performed subset analyses of SPM with regard to age, sex, radiotherapy used, and latency period. Results Among 33,720 patients, 1838 (5.45%) developed 2019 SPMs with an observed/expected (O/E) ratio of 1.11 [95% confidence interval (CI) = 1.06–1.16, p < 0.001] and an absolute excess risk of 18.16 per 10,000 population. The median time to first SPM from the time of diagnosis of gastric cancer was 46.9 months (range 6–239 months). Significant excess risk was observed for gastrointestinal malignancies [O/E ratio 1.71 (CI = 1.59–1.84, p < 0.001)], thyroid [O/E ratio 2.00 (CI = 1.37–2.8, p < 0.001)], and pancreatic cancer [O/E ratio 1.60 (CI = 1.29–21.96, p < 0.001)]. Risk of secondary melanoma, breast cancer, and prostate cancer was lower than in the general population. Conclusion The risk for SPMs is significantly increased in adults with gastric cancer compared to the general population.

Survival trends among patients with advanced renal cell carcinoma (RCC) in the United States.

422 Background: Since approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma. This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into survival benefit in population-based cohort. METHODS We analyzed the Surveillance, Epidemiology, and End Results (SEER) 18 registry database to compare 1- and 3-year relative survival rates among advanced RCC patients during 2001-2009, 2001-2004, and 2006-2009. We also evaluated the survival rates by age (<65 and ≥65 years) and sex. We used SEER*Stat software to analyze the data. RESULTS The total number of advanced RCC patients during 2001-2009, 2001-2004, and 2006-2009 were 7,055, 3,355 and 2,985 respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7± 0.6% and 10.0±0.4% respectively. The 1-year relative survival rates during 2001-2004 and 2006-2009 were 27.0±0.8% and 27.1±0.9%, (p value=1.3) respectively. Similarly, the 3-year survival rates during 2001-2004 and 2006-2009 were 10.1±0.6% and 9.6±0.8%, (p value=1.42), respectively. There was no significant difference in survival rates during 2001-2004 and 2006-2009 periods by age and sex. CONCLUSIONS This population based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents. As with other database analyses, limitations of this large study may be incomplete reporting practices and lack of data on treatment.