Sameer A Parikh

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (10)36.56 Total impact

  • 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;
  • International journal of dermatology 09/2014; · 1.18 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; · 5.79 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; · 4.94 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; · 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: 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; · 5.94 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; · 4.94 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. · 4.00 Impact Factor
  • Article: The reply.
    Sameer Parikh, Riddhi Shah, Prashant Kapoor
    The American journal of medicine 09/2010; 123(9):e21. · 5.30 Impact Factor
  • Sameer Parikh, Riddhi Shah, Prashant Kapoor
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    ABSTRACT: Portal vein thrombosis is a condition not infrequently encountered by clinicians. It results from a combination of local and systemic prothrombotic risk factors. The presentation of acute thrombosis varies widely from an asymptomatic state to presence of life-threatening intestinal ischemia and infarction. In the chronic stage, patients typically present with variceal bleeding or other complications of portal hypertension. Abdominal ultrasound color Doppler imaging has a 98% negative predictive value, and is considered the imaging modality of choice in diagnosing portal vein thrombosis. Controlled clinical trials to assist with clinical decision-making are lacking in both acute and chronic portal vein thrombosis. Oral anticoagulant therapy is initiated if the risks of bleeding are low, but long-term anticoagulation is generally not recommended in patients with concomitant hepatic cirrhosis. The roles of invasive therapeutic approaches such as thrombolysis and transjugular intrahepatic portosystemic shunt continue to evolve. This review conflates dissenting views into a rational approach of managing patients with portal vein thrombosis for the general internist.
    The American journal of medicine 02/2010; 123(2):111-9. · 5.30 Impact Factor
  • Sameer Parikh
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    ABSTRACT: Portal hypertension is one of the most important complications of chronic liver disease and accounts for significant morbidity and mortality. Measurement of the hepatic venous pressure gradient (HVPG) is a simple, invasive, and reproducible method of assessing portal venous pressure. Measurement of HVPG provides the clinician an estimate of the degree of intrahepatic portal flow resistance, guides therapy for variceal bleeding (primary and secondary prophylaxis), assesses feasibility of resection in patients with hepatocellular cancer, and predicts response to therapy of patients with chronic hepatitis C. Achieving hemodynamic targets of reducing the HVPG to <10 mmHg or a 20% reduction from baseline virtually eliminates complications related to portal hypertension from chronic liver disease. This review explores the role of HVPG measurement in the contemporary treatment of patients with cirrhosis and portal hypertension.
    Digestive Diseases and Sciences 10/2008; 54(6):1178-83. · 2.26 Impact Factor
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    Serge De Golovine, Sameer Parikh, Lee Lu
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    ABSTRACT: Polyarteritis nodosa is a rare necrotizing vasculitis that can be progressive and fatal, and its initial presenting symptom may be leg claudication due to peripheral vascular ischemia. To date, there have been fewer than ten case reports of polyarteritis nodosa presenting as peripheral vascular disease. We report a case of a 38-year-old man initially diagnosed to have premature peripheral vascular disease who presented 1 year later with symptoms consistent with giant cell arteritis and subsequently developed bowel ischemia leading to a fatal outcome. Based on the autopsy and the patient's clinical course, the final diagnosis was polyarteritis nodosa. This case illustrates the challenges in diagnosing polyarteritis nodosa and the importance of considering vasculitis in young patients presenting with atypical presentations of diseases such as peripheral vascular disease or giant cell arteritis.
    Journal of General Internal Medicine 07/2008; 23(9):1528-31. · 3.28 Impact Factor
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    ABSTRACT: Postpartum reversible cerebral vasoconstriction syndrome, also known as postpartum cerebral angiopathy, is clinically characterized by headache and focal neurologic deficits, and angiographically by transient, fully reversible cerebral vasoconstriction. A 26-year-old woman was brought to the emergency room with a 3-day history of confusion, agitation, and headache. She was 2 weeks postpartum. She went on to develop right leg weakness two days after admission. A cerebral angiogram showed diffuse irregularities of all intracerebral vessels, and MRI showed multiple acute infarcts. Her clinical condition improved significantly over the next several days without any intervention, and she was discharged. MRA 3 months after initial presentation was normal. It is important to consider this syndrome in the differential diagnosis in patients presenting with headache and focal neurologic deficits in the postpartum period.
    The American Journal of the Medical Sciences 10/2007; 334(3):222-4. · 1.33 Impact Factor
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    Sameer Parikh, David Hyman
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    ABSTRACT: Hepatocellular cancer is the third leading cause of cancer-related deaths worldwide. Its incidence has increased dramatically in the United States because of the spread of hepatitis C virus infection and is expected to increase for the next 2 decades. Hepatitis B virus, hepatitis C virus, and chronic heavy alcohol use leading to cirrhosis of the liver remain the most important causes. The diagnosis of hepatocellular cancer rests on a combination of radiologic, serologic, and histopathologic criteria. Liver transplantation is the only definitive treatment. Resection of the tumor and other percutaneous therapies are more commonly used in practice, because most hepatocellular cancers are detected at an advanced stage. Patients who are at high risk for the development of hepatocellular cancer should be screened with an ultrasound of the liver every 6 months. The prognosis is dependent on both the underlying liver function and the stage at which the tumor is diagnosed. The aim of this review is to familiarize internists in screening, diagnosis, and referral of patients with hepatocellular cancer in an appropriate and timely fashion.
    The American journal of medicine 04/2007; 120(3):194-202. · 5.30 Impact Factor
  • Critical Pathways in Cardiology: A Journal of Evidence-based Medicine. 01/2004; 3(3).