Concomitant Hematological Malignancy Research Articles

Risk factors for persistent fever in children with infectious mononucleosis.

Fever is a common symptom in children with infectious mononucleosis (IM). However, the significance of fever duration is poorly understood. This study aimed to analyze the risk factors for persistent fever in children with IM. Patients diagnosed with IM (aged <18 years; except those with concomitant hematological malignancies or tumor diseases) in a high-volume academic hospital in 2019 were reviewed from a prospectively maintained database. Comparison analysis was conducted between children with transient fever (≤7 days) and those with persistent fever (>7 days). The risk factors for persistent fever in children with IM were examined using binary logistic regression. Furthermore, the predictive ability of these risk factors was assessed and presented using a receiver operating characteristic (ROC) curve. Of the 184 children included in this study, 131 (71.96%) belonged to the transient fever group and 53 (28.04%) belonged to the persistent fever group (median age: 49 and 64 months, respectively; P = 0.093). Statistical significance was observed in hepatomegaly, alanine aminotransferase level, blood triglyceride level, and blood Epstein-Barr virus polymerase chain reaction (EBV-PCR) copy number (all P < 0.05). Binary logistic regression revealed that high blood triglyceride level was the risk factor for persistent fever in children with IM. High blood triglyceride level predicted persistent fever duration, with an area under the ROC curve of 0.73 and an optimal cutoff value of 1.315 mmol/L. High blood triglyceride level was the risk factor for persistent fever in children with IM. Thus, children with elevated levels of blood triglycerides need additional care. To diagnose IM, blood EBV-PCR is more useful than throat swab EBV-PCR.

Sepsis-associated coagulopathy in onco-hematology patients presenting with thrombocytopenia: a multicentric observational study

Coagulation disorders increase mortality rate during septic shock, but the impact of concomitant hematological malignancies remains unknown. The study assessed coagulation disorders in onco-hematological patients with thrombocytopenia (<100 G/L) admitted to ICU for septic shock. Among 146 included patients, 50 patients had lymphoma and 49 patients had acute leukemia. ICU mortality rate was 43.8% (n = 64). Median increase in prothrombin time (PT) at day(d) 1 was 4.7 s (IQR 3.2–7.9) in ICU survivors vs. 6.4 s (IQR 4.5–13.7; p < 0.01) in non-survivors. Fibrinogen kinetics (increase in fibrinogen levels between d1 and d2) was +0.55 (−0.22–1.55) vs. +0.10 g/L (−0.40–0.50; p = 0.03) in surviving and non-surviving patients, respectively. PT increase ≥6 s at d1 (OR 5.5; 95% CI 1.1–6.0; p = 0.03) and mechanical ventilation (OR 7.4; 95% CI 3.3–17.7; p < 0.001) were independently associated with ICU mortality. This study provides information and new ways to identify hematological patients with high-risk mortality.

COVID-19 vaccination in advanced skin cancer patients receiving systemic anticancer treatment: A prospective singlecenter study investigating seroconversion rates.

BackgroundCOVID-19 vaccination reduces risk of SARS-CoV-2 infection, COVID-19 severity and death. However, the rate of seroconversion after COVID-19 vaccination in cancer patients requiring systemic anticancer treatment is poorly investigated. The aim of the present study was to determine the rate of seroconversion after COVID-19 vaccination in advanced skin cancer patients under active systemic anticancer treatment.MethodsThis prospective single-center study of a consecutive sample of advanced skin cancer patients was performed from May 2020 until October 2021. Inclusion criteria were systemic treatment for advanced skin cancer, known COVID-19 vaccination status, repetitive anti-SARS-CoV-2-S IgG serum quantification and first and second COVID-19 vaccination. Primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination.ResultsOf 60 patients with advanced skin cancers, 52 patients (86.7%) received immune checkpoint inhibition (ICI), seven (11.7%) targeted agents (TT), one (1.7%) chemotherapy. Median follow-up time was 12.7 months. During study progress ten patients had died from skin cancer prior to vaccination completion, six patients were lost to follow-up and three patients had refused vaccination. 41 patients completed COVID-19 vaccination with two doses and known serological status. Of those, serum testing revealed n=3 patients (7.3%) as anti-SARS-CoV-2-S IgG positive prior to vaccination, n=32 patients (78.0%) showed a seroconversion, n=6 patients (14.6%) did not achieve a seroconversion. Patients failing serological response were immunocompromised due to concomitant hematological malignancy, previous chemotherapy or autoimmune disease requiring immunosuppressive comedications. Immunosuppressive comedication due to severe adverse events of ICI therapy did not impair seroconversion following COVID-19 vaccination. Of 41 completely vaccinated patients, 35 (85.4%) were under treatment with ICI, five (12.2%) with TT, and one (2.4%) with chemotherapy. 27 patients (65.9%) were treated non adjuvantly. Of these patients, 13 patients had achieved objective response (complete/partial response) as best tumor response (48.2%).Conclusion and relevanceRate of anti-SARS-CoV-2-S IgG seroconversion in advanced skin cancer patients under systemic anticancer treatment after complete COVID-19 vaccination is comparable to other cancer entities. An impaired serological response was observed in patients who were immunocompromised due to concomitant diseases or previous chemotherapies. Immunosuppressive comedication due to severe adverse events of ICI did not impair the serological response to COVID-19 vaccination.

Efficacy and safety of nivolumab for locally advanced or metastatic cutaneous cell carcinoma (NIVOSQUACS trial).

9528 Background: Cutaneous squamous cell carcinoma (cSCC) is the second most frequent skin cancer and considered as a tumor with strong immunogenicity. Consistently, immune checkpoint-inhibition with programmed death (PD)-1 antibodies has become the novel standard of care in the treatment of advanced cSCC. In this study, we evaluated efficacy and safety of the PD-1 antibody nivolumab in patients with locally advanced or metastatic cSCC, including individuals with concomitant hematological malignancies (CHM) – a highly vulnerable subgroup of cSCC patients typically excluded from clinical trials. Methods: This phase II, open-label, single-arm multicentre study included patients aged ≥ 18 years with histologically confirmed locally advanced and/or metastatic cSCC and at least one measurable lesion according to RECIST v1.1. Enrolled patients received nivolumab 240 mg intravenously over 30 min every 2 weeks for up to 2 years. A sample size of 31 patients was needed to provide 90% power to detect an objective response rate (ORR) of at least 12.6% after 24 weeks with a type I error of 5% assuming a dropout-rate of 15%. The primary endpoint was investigator assessed ORR as per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Between July 2017 and October 2020, 31 patients with advanced cSCC, including 11 patients with CHM, were enrolled and received at least one dose of nivolumab. The median age was 80 years (range 66-92) and the majority of patients was male (71%). Upon enrollment, 19.4% of patients had locally advanced, 51.6% loco-regional metastatic and 25.8% distant metastasic disease. Seven patients (22.6%) had received one prior systemic therapy for cSCC. At data-cut-off (March 2021; week-24 RECIST assessment completed in all available patients), five patients (16.1%) were still on treatment, one patient completed treatment per protocol, whereas 25 patients had discontinued therapy. Of 29 patients who were evaluable for response assessment, 12 patients achieved a partial and 7 a complete response, resulting in a best ORR of 65.2% (95% CI: 45.7% - 82.1%), a DCR of 68.9% (95% CI: 50.8%-82.7%) and a median PFS of 11.1 months (95% CI: 3.7 - 12.9). Treatment related adverse events occurred in 18 patients (58.1%) and led to nivolumab discontinuation in two patients (6.5%). Subgroup analysis of patients with CHM revealed a best ORR of 55.6% (95% CI: 21.2% - 86.3%), a DCR of 66.7% (95% CI: 35.4% -87.9%) and a median PFS of 10.9 months (95% CI: 0.6 - 21.4). Median OS in this subgroup was 20.7 months (95% CI: 6.5 - 35.0), whereas overall median OS was not reached. Conclusions: Nivolumab showed a robust antitumor-activity similar to other anti-PD-1 agents in advanced cSCC. Although ORR and OS were slightly reduced in patients with CHM, nivolumab proved effectiveness also in this subgroup while no new safety signals occurred. Clinical trial information: NCT04204837.

Survival Outcomes of Patients With Primary Mediastinal Germ Cell Tumors: A Retrospective Single-institutional Experience

Primary mediastinal non-seminomatous germ cell tumors (PMNSGCTs) are occasionally complicated by a hematologic malignancy, as with somatic-type malignant tumors called germ cell tumors with somatic-type malignancy (GCTSTM) and are known to have a poor prognosis. Data obtained between September 1997 and February 2020 for patients with mediastinal germ cell tumor at our institution were retrospectively analyzed. Key outcome measures included survival rates and the clinical features of non-seminoma cases. Of 16 patients, 9 had pure seminoma, and 7 had non-seminoma. At the median follow-up of 56.2 months, the 5-year survival rate was significantly higher in patients with seminoma (100%) than in those with non-seminoma (37%) (log-rank test, p=0.0153). Regarding PMNSGCT, two patients evolved into GCTSTM and three had concomitant hematological malignancies. Patients with PMNSGCTs, GCTSTM complications, and hematologic malignancies showed poor survival, suggesting the need for the development of treatment strategies.

The impact of comorbidity identification on outcomes in patients with pyoderma gangrenosum: A retrospective cohort study of previously hospitalized patients

The impact of comorbidity identification on outcomes in patients with pyoderma gangrenosum: A retrospective cohort study of previously hospitalized patients

Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients

BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer...

Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematologic Malignancies: A Systematic Literature Review

Many clinical and demographic factors can influence survival of patients with hematologic malignancies who have intracranial hemorrhages (ICHs). Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. Twelve articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days to 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematologic malignancy was 5days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low Glasgow Coma Scale scores at presentation, and ICH early in treatment course were associated with worse outcomes. Survival for patients with hematologic malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic factors, and correction of hematologic abnormalities essential to prevention and treatment of ICHs in this patient population.

Cerebral Venous Thrombosis in Hematological Malignancy: Balancing the Risks

Background and Aim: The coexistence of cerebral venous thrombosis (CVT) and hematological neoplasms is rare. Currently available therapeutic options raise problems concerning the balance of thrombotic and hemorrhagic risks. Our purpose is to characterize a series of cases of CVT and concomitant hematological malignancy, focusing on predisposing factors and treatment strategies. Methods: We performed a descriptive retrospective analysis of the cases of CVT and hematological neoplasms diagnosed in a tertiary center from 2006 to 2015. Results: From the 111 CVT cases diagnosed, only 7 coexisted with hematological malignancy (lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes). These included 4 women; median age was 44 years old. Median follow-up time was 72 days. The hematological condition was already known in 5 cases. Besides malignancy, we identified other prothrombotic conditions in all cases. Several anticoagulant strategies were used during the acute phase, after which 5 patients remained on warfarin indefinitely. One patient died due to cerebral hemorrhage during the acute phase. In the remaining 6 patients, there was no recurrence of CVT or other complications of anticoagulation. Conclusions: Although these results reiterate the role of hematological malignancy as predisposing factor to CVT, in all cases other factors contributed to CVT etiology, potentiating the risk. We report 1 death directly attributable to a fatal hemorrhagic complication of anticoagulation, evidencing the delicate balance of thrombotic and hemorrhagic risk. Nevertheless, most patients benefited of long-term anticoagulation, which proved a reasonable option. A multidisciplinary approach is paramount in making decisions regarding the time and type of anticoagulation.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Commonly Presents in the Setting of Prior or Concomitant Hematologic Malignancies (PCHM): Patient Characteristics and Outcomes in the Rapidly Evolving Modern Targeted Therapy Era

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Commonly Presents in the Setting of Prior or Concomitant Hematologic Malignancies (PCHM): Patient Characteristics and Outcomes in the Rapidly Evolving Modern Targeted Therapy Era

Bone Marrow Mastocytosis Is Independently Associated with Inferior Survival in Chronic Myelomonocytic Leukemia

Introduction: Systemic mastocytosis with associated hematologic neoplasm (SM-AHN) is defined by the presence of a concomitant hematologic malignancy with chronic myelomonocytic leukemia (CMML) being a particularly common partner. The overall survival of patients with SM-AHN is inferior to those with SM alone, even when matched for relevant prognostic covariates. However, the prognostic impact of mastocytosis in patients with CMML is unknown. Methods: CMML patients with concomitant mastocytosis were identified from the Moffitt Cancer Center CMML database. We assessed baseline demographic, clinical, and molecular findings and used Kaplan-Meier method to estimate overall survival (OS). The log-rank test was used to compare Kaplan-Meier curves, We then compared the SM-CMML cohort to a well-established institutional database of CMML patients. Baseline demographic and clinical variables were analyzed using GraphPad Prism and SPSS was used for Cox Regression Analysis. Results: Between 5/2004 and 5/2019 22 of 645 CMML patients (3.4%) were identified to have concomitant mastocytosis. The median follow-up for the 22 patients with SM-CMML was 51 months. Nine (41%) patients were diagnosed with de novo CMML prior to SM. In these cases, secondary SM-CMML occurred at a median time of 7 months after CMML diagnosis. Ten patients (45%) were diagnosed with CMML and SM concurrently and 3 (14%) were diagnosed with SM prior to CMML. Among 17 patients tested for KIT mutations, 12 were found to harbor a mutation. The remaining five patients did not undergo high-sensitivity KIT testing on a bone marrow aspirate. Eleven patients had extended gene sequencing performed with the most common additional mutations involving TET2 (45%), SRSF2 (55%), ASXL1 (27%), RAS (27%), DNMT3A (27%), and RUNX1 (27%). The median overall survival (OS) was estimated to be 38.6 months. Next, we compared this cohort of SM-CMML patients to a large, established database of CMML patients (excluding those with concomitant SM). Age at diagnosis, baseline white blood cell count, hemoglobin, and platelet count were well matched between the two groups. Applying the Mayo CMML Prognostic Model to the cohort of SM-CMML patients demonstrated that 32%, 41%, and 27% were low, intermediate and high risk, respectively. In the CMML cohort, 13%, 35%, and 51% were low, intermediate and high, risk respectively, suggesting the SM-CMML was more common in the lower-risk group (p=0.025). The median OS was similar between the two cohorts (median OS 31.3 vs 38.6 months, p = 0.43). However, multivariate analysis including Mayo Prognostic Scoring System, age &gt; 65, and SM component revealed all three variables to be independently associated with survival (HR 1.8, p &lt; 0.001; HR 1.7, p = 0.047; and HR 1.5, p 0.003, respectively). Assessing the impact of mastocytosis in low, intermediate, and high-risk groups separately, the inferior prognostic impact of mastocytosis was most prominent in high-risk patients (OS 19.6 mo vs. 5.4 mo; p = 0.049). Survival outcomes between SM-CMML and CMML were not statistically different in intermediate and low-risk groups (p = 0.47 and p = 0.19, respectively). Among 16 deaths in the SM-CMML cohort, cause of death was able to be assessed in 13 patients. Four (31%) patients died after transformation to acute myeloid leukemia (AML). These patients were either intermediate- or high-risk by Mayo Prognostic Model. Nine patients (69%) died due to multisystem organ failure due to progressive systemic mastocytosis without development of acute leukemia. Among these, 4 (44%) were low-risk, 3 (33%) were intermediate-risk, and 2 (22%) were high-risk. Conclusions: SM-CMML typically presented with lower-risk disease when graded by the Mayo CMML Prognostic Model. Compared head-to-head, OS was similar between SM-CMML and CMML; however multivariate analysis revealed the SM component to be a significant adverse prognostic factor. The presence of bone marrow mastocytosis is associated with inferior survival in high-risk CMML cases. Cause of death among SM-CMML patients was attributable to both progressive mastocytosis and transformation to AML. AML transformation was limited to intermediate- and high-risk group while progressive mastocytosis was seen across the risk spectrum. Future studies are warranted to determine if SM therapy can mitigate this outcome. Figure 1 Disclosures Kuykendall: Abbvie: Honoraria; Celgene: Honoraria; Incyte: Honoraria, Speakers Bureau; Janssen: Consultancy. Talati:Celgene: Honoraria; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria. Komrokji:DSI: Consultancy; Incyte: Consultancy; Agios: Consultancy; JAZZ: Consultancy; JAZZ: Speakers Bureau; Novartis: Speakers Bureau; pfizer: Consultancy; celgene: Consultancy.

Adverse Outcomes in Concurrent Sickle Cell Disease and Hematological Malignancies

Introduction:Case reports have suggested that there is an increased risk of hematological malignancies with sickle cell disease (SCD). We aimed to investigate the prevalence and mortality of select hematological malignancies, including: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), polycythemia vera (PV), essential thrombocytopenia (ET), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), primary myelofibrosis (PMF) in patients hospitalized with SCD.Methods:We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample to identify the hospitalizations with SCD using ICD-9 codes 282.6, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, 282.69 from 1999 to 2014. Cases were then stratified based on the concurrent presence of the above hematological malignancies. The percentages of patients with each type of hematological malignancy were obtained using Chi-square analysis. In addition, we compared outcomes between patients with and without SCD who had hematological malignancies. Bivariate analysis for in-hospital mortality percentage was performed using Chi-square test. Multivariate analysis to evaluate the risk of death during hospitalization was performed using Cox proportional hazard regression with alpha set at 0.05.Results:There were 307,424 admissions (weighted=1,513,168) with SCD. Within these admissions, 0.04% (n=516) were associated with AML, 0.05% (n=720) with HL, 0.02% (n=47) with ALL, 0.07% (n=1,028) with NHL, 0.69% (n=10,654) with ET, 0.01% (n=20) with PMF and 0.01% (n=18) with PV. The hazard ratio for mortality (95% C.I.) with SCD compared to without SCD was 3.60 (1.24-4.67) for AML (p <0.001), 4.56 (2.78-6.78) for ET (p <0.001), 2.37 (1.41-5.67) for NHL (p=0.003), 1.5 (0.8-4.5) for HL (p=0.08), 1.1 (0.5-3.2) for ALL (p=0.04), 1.3 (1.1-3.2) for PMF (p= 0.03) and 1.7 (0.6-2.9) for PV (p=0.05).Discussion:The most frequently encountered hematological malignancy in patients with SCD was ET, followed by NHL and then HL. After controlling for multiple confounders including age, race, sex, comorbidities and socioeconomic status, the hazard of death during hospitalization with SCD, ET, AML, NHL and ALL are significantly higher compared to those without SCD.While uncommonly encountered, concomitant hematological malignancy and SCD portends a significantly worse outcome, particularly in ET and AML. Potential explanations include iron overload from prior transfusions, increased infection risk due to asplenia and vascular damage from previous vaso-occlusive events. Newer advances in the management of SCD might improve subsequent outcomes in hematological malignancies. DisclosuresNo relevant conflicts of interest to declare.

Relapsing Polychondritis Can Be Characterized by Three Different Clinical Phenotypes: Analysis of a Recent Series of 142 Patients.

Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP. We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center. Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5- and 10-year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis. This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.

A case report of unusually long lag time between immunotactoid glomerulopathy (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.

BackgroundImmunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis.Case presentationA 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative disorder was initially found. In January 2014, the patient presented with a soft-palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6 cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up revealed complete remission of diffuse large B-cell lymphoma and resolution of proteinuria from the ITG.ConclusionAs we recognize that patients with ITG may develop hematopoietic neoplasms, close long-term monitoring is important. Moreover, treatment of the lymphoproliferative disorder can allow for complete remission of ITG.

First Highly Promising Experiences With Implantations of a Gas Driven Pump for Prostacyclin Therapy in Patients Even With Severe Pulmonary Hypertension and Concomitant Hematologic Malignancy

First Highly Promising Experiences With Implantations of a Gas Driven Pump for Prostacyclin Therapy in Patients Even With Severe Pulmonary Hypertension and Concomitant Hematologic Malignancy

Chronic Hepatitis C Infection and Hematologic Malignancies: Is There an Association?.

BACKGROUNDMore than 4 million people in the United States are chronically infected with hepatitis C virus (HCV) and approximately 800,000 will develop liver cirrhosis or present with several other extrahepatic conditions such as porphyria cutanea tarda, lichen planus, vitiligo, mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and bone marrow hypoplasia. Several studies with relatively small convenience samples of HCV-infected patients seen at referral centers present controversial results regarding the association between HCV infection and B-cell lymphomas.METHODSUsing the computerized database of the Department of Veterans Affairs, Fresno, California, we carried out a cross-sectional study to examine whether B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies might be associated with chronic HCV infection. We examined all cases of chronic HCV infected patients (n=992) diagnosed between 1991 and 2004 and randomly matched control subjects HCV naïve (n=1,929).Demographic DistribuitionCases (n=992)Controls (n=1,929)Alive at enrollment880 (88.7%)1,761 (91.3%)Age (years)53.1353.14gender (male)869 (98.8%)1,725 (98%)Period of military service (Vietnam Era)578 (66%)1,149 (62%)Exposure to Agent Orange12 (2%)35 (2%)RESULTSAn increased prevalence of hematologic malignancies was found among the chronic HCV infected patients compared to the control group with an odds ratio (OR) of 3.4 (95% confidence interval [95%CI]=1.4–10, p=0.009). The prevalence of NHL (OR=4.2, 95%CI=0.7–22, p=0.1), Hodgkin's lymphoma (p=0.1), myeloproliferative disorders (OR=4.2, 95%CI=0.7–22, p=0.1), myelodysplastic syndrome (p=0.6) and myeloma (p=0.3) was each independently statistically not significant. The chronic HCV infected group showed a prevalence of 2% for hepatocellular carcinoma (p<0.0001) and had a significantly higher rate of HIV co-infection compared to the control group (OR=6, 95%CI=3–13, p<0.0001). However, none of the chronic HCV and HIV co-infected patients presented a concomitant hematologic malignancy. The overall mortality rate in the chronic HCV infected patients was 11.3% and of the control group 8.7% (OR=1.3, 95%CI=1–1.7, p=0.028). Patients with chronic HCV infection died significantly earlier (mean age 56.7 years) compared to the subjects in the control group (mean age 63.5 years) (p<0.0001).Chronic HCV Infection and Hematologic MalignanciesCases n=880 (%, 95%CI)Controls n=1,761 (%, 95%CI)OR95%CIpNHL4 (0.5%, 0.2–1.2)2 (0.1%, 0.04–0.4)4.20.7–220.1Hodgkin's lymphoma2 (0.3%, 0.07–0.8)0 (0%, 0.001–0.2)--0.1Myeloproliferative disorders4 (0.5%, 0.2–1.2)2 (0.1%, 0.04–0.4)4.20.7–220.1Myelodysplastic syndromes0 (0%, 0.003–0.4)2 (0.1%, 0.04–0.4)--0.6Multiple Myeloma1 (0.1%, 0.03–0.6)0 (0%, 0.001–0.2)--0.3Overall Hematologic Malignancies11 (1.3%, 0.7–2.2)6 (0.34%, 0.2–0.7)3.41.4–100.009CONCLUSIONSWe report the prevalence of several hematologic malignancies in chronic HCV-infected veterans. Our study suggests that chronic HCV infection is a significant risk factor for lymphatic and stem-cell malignancies. Further larger studies are required to confirm this finding.

Intense immunosuppression and stem-cell transplantation for patients with severe rheumatic autoimmune disease: a review.

Intense immunosuppression plus stem-cell transplantation (SCT) has emerged as a new treatment modality for patients with refractory, severe rheumatic autoimmune disease. Its rationale is based on eliminating autoaggressive lymphocytes by lympho- or myeloablative conditioning followed by stem-cell rescue. Preclinical studies in animal models of autoimmune disease and observations in patients with rheumatoid arthritis (RA) who were cured after allogeneic bone marrow transplantation for concomitant hematologic malignancy have provided support for the concept. The authors reviewed the results of recent phase I/II studies and data from the EBMT/EULAR Registry on more than 400 patients with autoimmune diseases including RA, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and juvenile idiopathic arthritis (JIA). Toxicity resulting from stem-cell grafting depended on underlying disease and the intensity of the conditioning regimen. Treatment-related mortality was low in RA (1.4%) but relatively high (>10%) in patients with JIA, SLE, and SSc, possibly related to visceral involvement in these patients. With the application of uniform and strict criteria, safety has improved. Long-term remissions up to 4 years have been observed in SSc and JIA, while relatively more relapses have occurred in patients with SLE and RA. Sensitivity to antirheumatic drugs was restored in RA and SLE patients, however, resulting in improved disease control. Intense immunosuppression and SCT may be an effective therapy for selected patients with severe rheumatic autoimmune disease. Its merits need to be proven via multicenter phase III studies by comparing efficacy and safety with conventional therapy.