Sameer A Parikh

Mayo Clinic - Scottsdale, Scottsdale, Arizona, United States

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Publications (14)62.32 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival. Cancer 2015;000:000-000. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 04/2015; DOI:10.1002/cncr.29438 · 4.90 Impact Factor
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    ABSTRACT: To evaluate the impact of approval of ibrutinib and idelalisib on pharmaceutical costs in the treatment of chronic lymphocytic leukemia (CLL) at the societal level and assess individual out-of-pocket costs under Medicare Part D. Average wholesale price of commonly used CLL treatment regimens was ascertained from national registries. Using the population of Olmsted County, Minnesota, we identified the proportion of patients with newly diagnosed CLL who experience progression to the point of requiring treatment. Using these data, total pharmaceutical cost over a 10-year period after diagnosis was estimated for a hypothetic cohort of 100 newly diagnosed patients under three scenarios: before approval of ibrutinib and idelalisib (historical scenario), after approval of ibrutinib and idelalisib as salvage therapy (current scenarios A and B), and assuming use of ibrutinib as first-line treatment (potential future scenario). Estimated 10-year pharmaceutical costs for 100 newly diagnosed patients were as follows: $4,565,929 (approximately $45,659 per newly diagnosed patient and $157,446 per treated patient) for the historical scenario, $7,794,843 (approximately $77,948 per newly diagnosed patient and $268,788 per treated patient) for current scenario A, $6,309,162 (approximately $63,092 per newly diagnosed patient and $217,557 per treated patient) for current scenario B, and $16,414,055 (approximately $164,141 per newly diagnosed patient and $566,002 per treated patient) for the potential future scenario. Total out-of-pocket cost for 100 patients with newly diagnosed CLL under Medicare Part D increased from $9,426 under the historical scenario (approximately $325 per treated patient) to $363,830 and $255,051 under current scenarios A and B (approximately $8,800 to $12,500 per treated patient) and to $1,031,367 (approximately $35,564 per treated patient) under the future scenario. Although ibrutinib and idelalisib are profound treatment advances, they will dramatically increase individual out-of-pocket and societal costs of caring for patients with CLL. These cost considerations may undermine the potential promise of these agents by limiting access and reducing adherence. Copyright © 2015 by American Society of Clinical Oncology.
    Journal of Oncology Practice 03/2015; DOI:10.1200/JOP.2014.002469
  • Blood 03/2015; 125(10):1676-8. DOI:10.1182/blood-2014-12-610782 · 9.78 Impact Factor
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    ABSTRACT: Although transformation to Hodgkin lymphoma (HL) is a recognized complication in patients with chronic lymphocytic leukemia (CLL), its incidence, clinical characteristics and outcomes are not well defined.We used the Mayo Clinic CLL and Lymphoma Databases to identify CLL patients who developed biopsy-proven HL (CLL/HL) on follow-up, as well as cases of de novo HL (i.e., without prior CLL). Among 3887 CLL patients seen at Mayo Clinic from January 1995 through August 2011, 26 (0.7%) developed HL. In a nested cohort of 2465 newly diagnosed CLL patients followed prospectively, the incidence of HL was 0.05%/year (10 year risk=0.5%). The median overall survival (OS) from date of HL diagnosis in patients with CLL/HL was 3.9 years compared to not reached for de novo HL patients (n=709) seen during the same time interval (p<0.001). The shorter OS of CLL/HL patients persisted after adjusting for differences in age and Ann Arbor stage of disease. The International Prognostic score (IPS) developed for de novo HL stratified prognosis among CLL/HL patients with median survival of not reached, 6.2 years, 2.4 years and 0.3 years (p=0.006) for those with IPS scores of ≤2, 3, 4 and ≥5, respectively. In summary, approximately 1 of every 200 CLL patients will develop HL within 10 years. Survival after HL diagnosis in patients with CLL is shorter than de novo HL patients. The IPS for de novo HL may be useful for stratifying survival in CLL/HL patients. This article is protected by copyright. All rights reserved.
    American Journal of Hematology 01/2015; 90(4). DOI:10.1002/ajh.23939 · 3.48 Impact Factor
  • Sameer A Parikh, Tait D Shanafelt
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    ABSTRACT: Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) to a more aggressive B-cell lymphoma, most commonly diffuse large B-cell lymphoma. Approximately 5 - 10 % of CLL patients develop this complication during long-term follow-up. Traditional risk factors for future RS include clinical (advanced Rai stage), biological (ZAP-70, CD38, CD49d) and genetic (del17p, del11q) characteristics at the time of CLL diagnosis. The impact of CLL therapy (purine-nucleoside analogue and/or alkylator-based chemoimmunotherapy and kinase inhibitor therapy) on the risk of RS remains controversial. Both heritable (germline) and acquired (somatic) genetic mutations contribute to risk of RS. Germline polymorphisms in genes related to CD38, LRF4, and BCL-2 have been implicated in the development of RS. Somatic mutations contributing to the development of RS include TP53 disruption, c-myc activation, CDKN2A loss and NOTCH1 mutations. This review summarizes recent advances in our understanding of the biological and genetic factors contributing to RS in CLL patients.
    Current Hematologic Malignancy Reports 09/2014; 9(3). DOI:10.1007/s11899-014-0223-4 · 2.29 Impact Factor
  • International journal of dermatology 09/2014; DOI:10.1111/ijd.12682 · 1.23 Impact Factor
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    ABSTRACT: Objective To describe the prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. Patients and Methods The study population consisted of a consecutive cohort of adult (age ≥18 years) patients treated at Mayo Clinic in Rochester, Minnesota, from January 1, 1996, through December 31, 2011, in whom a diagnosis of HLH was suspected and subsequently confirmed by retrospective review using the HLH-04 diagnostic criteria. Results Of 250 adult patients suspected of having HLH, 62 met the HLH-04 diagnostic criteria and were included in the final analysis. The median age was 49 years (range, 18-87 years), and 42 (68%) were male. The underlying cause of HLH was malignant tumor in 32 patients (52%), infection in 21 patients (34%), autoimmune disorder in 5 patients (8%), and idiopathic disease in 4 patients (6%). After a median follow-up of 42 months, 41 patients (66%) had died. The median overall survival of the entire cohort was 2.1 months. The median overall survival of patients with tumor–associated HLH was 1.4 months compared with 22.8 months for patients with non-tumor–associated HLH (P=.01). The presence of a malignant tumor and hypoalbuminemia were significant predictors of inferior survival on multivariate analysis. Conclusion In this large series of adults with secondary HLH treated at a single tertiary care center, patients with low serum albumin levels and tumor–associated HLH had a markedly worse survival. Hemophagocytic lymphohistiocytosis remains elusive and challenging to clinicians who must maintain a high index of suspicion. The recent discovery of several novel diagnostic and therapeutic modalities may improve outcomes of adult patients with HLH.
    Mayo Clinic Proceedings 04/2014; DOI:10.1016/j.mayocp.2013.12.012 · 5.81 Impact Factor
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    ABSTRACT: Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic stem cell disorder with myelodysplastic and myeloproliferative overlap features, and an inherent tendency to transform to acute myeloid leukaemia. Approximately 30% of patients present with clonal cytogenetic abnormalities, while almost 90% have molecular aberrations involving epigenetic regulation, the spliceosome component machinery, tumour suppressor genes and transcription factors/regulators. Numerous prognostic models exist for CMML, with more recent models incorporating prognostic mutations, such as those involving ASXL1. Other variables that seem to consistently affect outcomes include the degree of leucocytosis/monocytosis, anaemia and thrombocytopenia. Allogeneic stem cell transplant remains the only curative option for CMML, while hypomethylating agents can be used for transplant-ineligible patients or those without suitable stem cell sources. Targeting biological pathways activated in CMML offers potential hope for more effective and less toxic therapies.
    British Journal of Haematology 01/2014; DOI:10.1111/bjh.12756 · 4.96 Impact Factor
  • Sameer A Parikh, Neil E Kay, Tait D Shanafelt
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    ABSTRACT: Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RS occurs in approximately 2-10% of CLL patients during the course of their disease, with a transformation rate of 0.5-1% per year. A combination of germline genetic characteristics, clinical features (e.g. advanced Rai stage), biologic (ZAP-70+, CD38+ and CD49d+) and somatic genetic (del17p13.1 or del11q23.1) characteristics of CLL B-cells, and certain CLL therapies are associated with higher risk of RS. Recent studies have also identified the crucial role of CDKN2A loss, TP53 disruption, C-MYC activation, and NOTCH1 mutations in the transformation from CLL to RS. An excisional lymph node biopsy is considered the gold standard for diagnosis of RS where (18)F-fluorodeoxyglucose positron emission tomography (PET) scan can help inform the optimal site for biopsy. Approximately 80% of DLBCL cases in patients with CLL are clonally related to the underlying CLL and the median survival for these patients is approximately 1 year. In contrast, the remaining 20% of patients have a clonally unrelated DLBCL and have a prognosis similar to that of de novo DLBCL. For patients with clonally related DLBCL, induction therapy with either an anthracycline- or platinum-based regimen is the standard approach. Post remission stem cell transplantation should be considered for appropriate patients. This article summarizes our approach to the clinical management of CLL patients who develop RS.
    Blood 01/2014; DOI:10.1182/blood-2013-11-516229 · 9.78 Impact Factor
  • Sameer A Parikh, Neil E Kay, Tait D Shanafelt
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    ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) is a clonal B-cell disorder characterized by less than 5 × 109/L B lympho- cytes in the peripheral blood, with a characteristic immunophe- notype and no lymphadenopathy or organomegaly. The vast majority of MBL cases express the immunophenotype of chronic lymphocytic leukemia (CLL; CLL-like MBL), although non-CLL MBL also exists. CLL-like MBL, which is the focus of this review, is divided into low-count MBL (median B-cell count: 0.001 × 109/L, typically identified in population-based screening studies using highly sensitive flow cytometry assays) and high-count MBL (clinical MBL, median B-cell count: 2.9 × 109/L, typically identi- fied during the workup of low-level lymphocytosis). Low-count MBL has an exceedingly small risk of progression to CLL, and these patients do not require any specific follow-up. In contrast, patients with high-count MBL have a 1% to 2% per year risk of progression to CLL requiring therapy, as well as a higher risk of infectious complications and secondary malignancies. Although the overall survival of high-count MBL patients collectively is similar to the age- and sex-matched general population, 5-year survival for high-count MBL with higher-risk biologic parameters appears to be slightly lower than that of the general population. This review summarizes key concepts in the classification, diag- nosis, and biology of CLL-like MBL and addresses several impor- tant issues in clinical management. [Editor's Note: Corrections were made to this article on February 12, 2014.].
    Clinical advances in hematology & oncology: H&O 11/2013; 11(11):720-729.
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    ABSTRACT: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly differentiated squamous cell carcinoma that is characterized by a balanced translocation between chromosomes 15 and 19 [t(15;19)(q14;p13.1)]. This genetic aberration results in the fusion of the NUT gene on chromosome 15 to the bromodomain containing 4 (BRD4) gene on chromosome 19. The resultant BRD4-NUT fusion oncogene leads to global hypoacetylation and transcriptional repression of genes required for differentiation." Although it was first reported in 1991 by Kubonishi et al., awareness of this condition remains low and the diagnosis is overlooked initially in a number of patients. A 36-year-old man complained of cough and right-sided chest pain for 3 weeks before presentation. Imaging studies revealed a right hilar mass, and a bronchoscopic biopsy was consistent with an aggressive poorly differentiated neoplasm. A combination of cisplatin, ifosfamide, and etoposide was administered for two cycles without any improvement. A repeat core biopsy showed focal squamous differentiation; and given the clinical presentation along with the histologic features, NMC was considered in the differential diagnosis. Immunohistochemical staining for NUT was positive, and dual-color break-apart fluorescence in situ hybridization demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. Our patient was subsequently enrolled on a phase 1 clinical trial of a novel, orally bioavailable bromodomain and extra terminal inhibitor, GSK525762 (NCT01587703). This report illustrates the challenges in diagnosing this rare malignancy, and highlights new treatment options for these patients.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2013; 8(10):1335-8. DOI:10.1097/JTO.0b013e3182a00f41 · 5.80 Impact Factor
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    ABSTRACT: The clinical characteristics and outcomes of younger (≤55 years) patients with chronic lymphocytic leukemia in the era of modern prognostic biomarkers and chemoimmunotherapy are not well understood. Baseline characteristics and outcomes of patients with chronic lymphocytic leukemia ≤55 years who were seen at Mayo Clinic between 1/1995 and 4/2012 were compared with those >55 years. Overall survival of patients ≤55 was compared to age- and sex-matched normal population. The characteristics of 844 newly diagnosed chronic lymphocytic leukemia patients ≤55 years (median, 50 years) were compared to 2324 patients >55 years (median, 67 years). Younger patients were more likely to be Rai stage I or II (p<0.0001), IGHV unmutated (p=0.002) and ZAP-70 positive (p=0.009). These differences became more pronounced when ≤55 age group was sub-stratified into age ≤45, 46-50 and 51-55 years. After a median follow-up of 5.5 years, 426 (51%) patients ≤55 received treatment, and 192 (23%) had died. Patients ≤55 had a shorter time to first treatment (4.0 years vs. 5.2 years; p=0.001) but longer survival (12.5 years vs. 9.5 years; p<0.0001) compared to patients >55 yrs. However, patients ≤55 had significantly shorter survival than age- and sex-matched normal population (12.5 years vs. not reached; p<0.0001). Our study is the first comprehensive analysis of younger chronic lymphocytic leukemia patients in the modern era. Adverse prognostic markers appear more common among young patients. Although the survival of young chronic lymphocytic leukemia patients is longer than those >55, their survival relative to the age- and sex-matched normal population is profoundly shortened.
    Haematologica 08/2013; DOI:10.3324/haematol.2013.086066 · 5.87 Impact Factor
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    ABSTRACT: Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy-proven RS during follow-up were identified. After a median follow-up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P < 0·001), high-risk genetic abnormalitites on fluorescence in situ hybridization (P < 0·0001), unmutated IGHV (P = 0·003), and expression of ZAP70 (P = 0·02) and CD38 (P = 0·001). The rate of RS doubled in patients after treatment for CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed.
    British Journal of Haematology 07/2013; 162(6). DOI:10.1111/bjh.12458 · 4.96 Impact Factor
  • Sameer A Parikh, Ayalew Tefferi
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    ABSTRACT: DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is classified as a myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization classification of hematopoietic tumors. It is characterized by absolute monocytosis (>1 × 10(9) L(-1) ) in the peripheral blood that persists for at least 3 months. Patients may present with symptoms related to cytopenias and/or an underlying hypercatabolic state with drenching night sweats, splenomegaly, and weight loss. DIAGNOSIS: The diagnosis of CMML rests on a combination of morphologic, histopathologic, and chromosomal abnormalities in the bone marrow, after careful exclusion of other conditions (both malignant and nonmalignant) that can cause monocytosis. Numerous molecular abnormalities have been recently recognized in patients with CMML-unfortunately, no single pathognomonic finding specific to CMML has been identified thus far. RISK STRATIFICATION: The International Prognostic Scoring System for myelodysplastic syndrome (MDS) cannot be used to risk stratify patients with CMML because this model excluded patients with a leukocyte count >12 × 10(9) L(-1) . Other risk stratification models such as the MD Anderson prognostic score and Dusseldorf score have been published. In the only model that took karyotype into account, bone marrow blasts ≥ 10%, leukocyte count ≥ 13 × 10(9) L(-1) , hemoglobin < 10 g/dL, platelet count < 100 × 10(9) L(-1) , and presence of trisomy 8, abnormalities of chromosome 7, or complex karyotype were found to be independent predictors of adverse survival. RISK-ADAPTED THERAPY: The Food and Drug Administration has approved azacitidine and decitabine for the treatment of patients with CMML based on two pivotal trials in MDS. Novel classes of agents including immunomodulatory drugs, nucleoside analogs, and small-molecule tyrosine kinase inhibitors are being investigated in the treatment of CMML. With the advent of reduced intensity conditioning, an allogeneic stem cell transplant has also become a viable option for a subset of patients.
    American Journal of Hematology 06/2012; 87(6):610-9. DOI:10.1002/ajh.23203 · 3.48 Impact Factor