The risk of malignancy and its incidence in early rheumatoid arthritis patients treated with biologic DMARDs

Background

Treatment with disease-modifying anti-rheumatic drugs (DMARDs) has raised concerns about the risk of malignancies in rheumatoid arthritis (RA) patients. However, the association between biologic DMARDs (bDMARDs) and malignancy in previous reports remains controversial. Therefore we aimed to estimate the incidence of malignancy in early RA patients and to evaluate the relative risk of malignancy with use of bDMARDs.

Methods

A retrospective cohort of incident RA patients was established using the Korean National Claims Database. Among a total of 14,081 RA patients identified, 1684 patients with a history of malignancy were excluded. We calculated the incidence rate of overall and individual malignancies. The standardized incidence ratio (SIR) of malignancies in bDMARD users was compared to that in nonusers. Multivariable logistic regression analysis was used to evaluate the impact of bDMARDs on the development of malignancies in early RA patients.

Results

A total of 12,397 early RA patients without a history of malignancy were enrolled. During 41,599 person-years (PY) of follow-up, 725 malignancies developed in 561 patients (174.3/10,000 PY) and 21 hematologic malignancies developed (5.0/10,000 PY). Patients treated with bDMARDs had a significantly lower incidence of overall malignancy compared to those not treated with bDMARDs (SIR 0.45 (95% CI 0.28–0.70)). However, this relationship was not significant with regard to hematologic malignancies (SIR 2.65 (95% CI 0.55–7.76)). On multivariable analysis, bDMARD use was a protective factor against the development of overall malignancy (odds ratio 0.42 (95% CI 0.25–0.73)). However, bDMARD use had no significant protective effect against the development of hematologic malignancies (odds ratio 1.69 (95% CI 0.38–7.59)).

Conclusions

In early RA patients, bDMARD use decreases the overall risk of developing malignancies; however, it does not affect the risk of developing hematologic malignancies.

     

Time Trend of Multiple Myeloma and Associated Secondary Primary Malignancies in Asian Patients: A Taiwan Population–Based Study

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78–1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79–21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.     

Plasma levels and urinary excretion of amino acids by subjects with renal calculi

Plasma levels and urinary amino acid excretions were estimated by high-performance liquid chromatography in 15 control subjects and 36 stone formers (SFs) classified according to the stone type: (1) 22 cases with calcium oxalate stones; (2) four cases with pure uric acid stones; (3) 10 cases with magnesium-ammonium phosphate stones, either pure or mixed with apatite. Some types of stones (namely oxalate and uric acid calculi) are mainly formed as a result of a metabolic deficiency that may affect the amino acid metabolism, and thus may be reflected in the urinary amino acid pattern. Data demonstrated clearly that there is a general tendency towards decreased amino acid excretions in all SFs with all types of stones. As a whole, one can observe a higher percentage of patients with calcium oxalate and phosphate calculosis, who have low urine excretions of amino acids; about 50% are the SFs with lower urine excretion of serine, glycine, taurine and i-leucine; the high percentage of patients with CaOX calculi shows lower urine excretions of tyrosine and ornithine.     

成人原发肾病综合征患者血尿酸与血脂代谢的关系

目的:研究成人原发肾病综合征(PNS)患者高尿酸血症的患病率及其与血脂代谢的关系。方法:将109例成人PNS患者根据其尿酸水平分为高尿酸血症组与血尿酸正常组,检测患者的血脂、血清脂蛋白、ALB及24小时尿蛋白定量,分析成人PNS患者高尿酸血症的患病率,比较高尿酸血症组与血尿酸正常组PNS患者的一般情况及血脂水平,并分析PNS患者血尿酸水平的相关因素。结果:成人PNS患者高尿酸血症的发病率为24.77%;高尿酸血症组患者TG及24小时尿蛋白定量水平明显高于血尿酸正常组(P0.01),两组患者TC、LDL-C、HDL-C、Apo AI及Apo B比较差异无统计学意义(P0.05);成人PNS患者血尿酸水平与TG及24小时尿蛋白定量水平呈正相关(r=0.350,P=0.001;r=0.533,P=0.014),与TC、LDL-C、HDL-C及ALB无明显相关性(P0.05)。结论:成人PNS患者高尿酸血症的发生率较高,高尿酸血症患者具有更高的TG及尿蛋白水平,且成人PNS患者血尿酸水平与TG及24小时尿蛋白定量具有相关性,应高度重视成人PNS患者的血尿酸水平。     

Phase I study of recombinant human tumor necrosis factor-alpha in patients with advanced malignancies

A clinical phase I trial with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was performed in 30 patients with advanced malignancies. The maximal tolerated dose (MTD) by 3 times weekly intramuscular (i.m.) application was 150 micrograms m-2. Main subjective toxicities including chills, fever, hypotension, fatigue, and anorexia were dose-related. In addition, transient changes in hematologic parameters and lipid metabolism were noted. Two out of 25 evaluated patients showed a minor tumor response after eight weeks of therapy. There was evidence for an improvement of in vivo immuneresponsiveness as revealed from positive delayed type hypersensitivity (DTH) skin tests of 3 out of 6 pretherapeutically anergic patients. We conclude from this phase I trial that rTNF-alpha can be safely administered at doses up to 150 micrograms m-2 i.m., 3 times weekly, without evidence of cumulative toxicity in long-term treatment.     

Hyperuricemia in Pediatric Malignancies Before Treatment

The objective of this study was to clarify the prevalence and characteristics of hyperuricemia in various pediatric malignancies before the initiation of treatment. We conducted a retrospective analysis of 119 children with various newly diagnosed malignancies between April 2000 and March 2010. On the basis of the reference values previously established in our laboratory, hyperuricemia was defined as uric acid (UA) levels above 2 standard deviations (s.d.) over the mean values at each age. Thirty-six patients (30.3%) showed hyperuricemia. Hyperuricemia was more common in male patients (36.8%) than in female patients (21.6%). The prevalence of hyperuricemia was highest in patients with lymphoma followed by those with acute lymphoblastic leukemia (ALL). When the study population was divided into hyperuricemia-negative and -positive populations, blood urea nitrogen, creatinine, and lactate dehydrogenase levels, and white blood cell counts (only in leukemia) were found to be significantly higher in the latter group by a univariate analysis. This study highlights useful information for identifying patients with malignancies at risk for tumor lysis syndrome (TLS) before starting chemotherapy.     

Hyperuricemia in pediatric malignancies before treatment

The objective of this study was to clarify the prevalence and characteristics of hyperuricemia in various pediatric malignancies before the initiation of treatment. We conducted a retrospective analysis of 119 children with various newly diagnosed malignancies between April 2000 and March 2010. On the basis of the reference values previously established in our laboratory, hyperuricemia was defined as uric acid (UA) levels above 2 standard deviations (s.d.) over the mean values at each age. Thirty-six patients (30.3%) showed hyperuricemia. Hyperuricemia was more common in male patients (36.8%) than in female patients (21.6%). The prevalence of hyperuricemia was highest in patients with lymphoma followed by those with acute lymphoblastic leukemia (ALL). When the study population was divided into hyperuricemia-negative and -positive populations, blood urea nitrogen, creatinine, and lactate dehydrogenase levels, and white blood cell counts (only in leukemia) were found to be significantly higher in the latter group by a univariate analysis. This study highlights useful information for identifying patients with malignancies at risk for tumor lysis syndrome (TLS) before starting chemotherapy.     

Association of plasma manganese levels with chronic renal failure

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn.     

Intravascular clotting activation and bleeding in patients with hematologic malignancies

The association between thrombosis, bleeding and neoplastic disease is well recognized. There are distinctive features of the thrombotic and bleeding complications associated with specific hematologic malignancies. A number of procoagulants can initiate intravascular clotting including tissue factor, cancer procoagulant and interleukin-1. The hematologic malignancy most often associated with intravascular clotting and bleeding is acute promyelocytic leukemia. The pathogenesis of the life-threatening bleeding disorder associated with this uncommon subtype of acute myeloid leukemia (AML) is complex and involves disseminated intravascular coagulation, fibrinolysis and proteolysis. Both all-trans retinoic acid and arsenic trioxide result in relatively rapid resolution of the coagulopathy. Intravascular clotting may also be induced by hyperleukocytosis in AML and by the hyperviscosity syndrome observed in multiple myeloma and Waldenstr?m's macroglobulinemia. In the setting of hematologic malignancies, when thromboembolic complications occur, the presence of comorbid thrombophilic conditions should be excluded. Abnormal platelet production and function contribute to the development of thrombosis in patients with myeloproliferative disorders. The Budd-Chiari syndrome may be observed in patients with myeloproliferative disorders. A number of medications have thrombogenic potential, including corticosteroids, thalidomide, L-asparaginase, all-trans retinoic acid and arsenic trioxide.     

Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia

BACKGROUND: The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic + cells in patients with hematologic malignancies and bad prognosis. Methods Thirty-three patients [median age 42 years, range 23-55 years, diagnosis AML/myelodysplastic syndrome (MDS) 14, ALL nine, CML seven and multiple myeloma (MM) three] received myeloablative conditioning followed by infusion of selected CD34+ cells from matched unrelated donors (31) or HLA-identical siblings (two). Early donor lymphocyte infusions (DLI; 0.5 and 1.0 x 10(6) CD3+ cells/kg) were given while patients were on immunosuppressive therapy. RESULTS: Ninety-seven per cent of patients engrafted and 24 of 29 patients surviving more than 30 days received at least one pre-emptive DLI. Three patients (10%) developed acute (a)GvHD (two grade I-II, one grade III-IV) spontaneously, and 16 patients (67%) developed aGvHD after DLI (12 grade I-II, four grade III-IV). Eight of 24 evaluable patients developed chronic (c)GvHD (33%, six limited, two extensive). After a median follow-up of 590 days (range 138-1610 days) 18 patients were alive (55%), 16 in complete remission (CR), one in hematologic and one in molecular relapse. Seven patients died after relapse (21%) and eight died from transplantation-related causes (24%). Patients with myeloid malignancies had a significantly better survival than patients with ALL or MM (74%+/-10 vs. 30%+/-13, P<0.05). DISCUSSION: Early pre-emptive low-dose DLI following transplantation of selected CD34+ cells from unrelated donors after myeloablative conditioning is feasible and effective without undue toxicity, especially in patients with myeloid malignancies.     

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity.     

Management of Hyperuricemia with Rasburicase Review

Tumor lysis syndrome (TLS) is a serious complication in patients with hematological malignancies. Massive lysis of tumor cells can lead to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic disturbances may result in renal failure, because of precipitation of uric acid crystals and calcium phosphate salts in the kidney. The standard prophylaxis or treatment of hyperuricemia consists of decreasing uric acid production with allopurinol and facilitating its excretion by urinary alkalinization and hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the conversion of hypoxanthine and xanthine into uric acid. An alternative treatment is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5–10 times more soluble than uric acid and is therefore excreted easily. In several clinical trials rasburicase, the recombinant form of urate oxidase, has shown to be very effective in preventing and treating hyperuricemia. Rasburicase, in contrast with the non‐recombinant form of urate oxidase uricozyme, is associated with a low incidence of hypersensitivity reactions. In addition to the demonstrated clinical benefit, rasburicase also proved to be a cost‐effective option in the management of hyperuricemia.     

Management of hyperuricemia with rasburicase review

Tumor lysis syndrome (TLS) is a serious complication in patients with hematological malignancies. Massive lysis of tumor cells can lead to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic disturbances may result in renal failure, because of precipitation of uric acid crystals and calcium phosphate salts in the kidney. The standard prophylaxis or treatment of hyperuricemia consists of decreasing uric acid production with allopurinol and facilitating its excretion by urinary alkalinization and hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the conversion of hypoxanthine and xanthine into uric acid. An alternative treatment is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5-10 times more soluble than uric acid and is therefore excreted easily. In several clinical trials rasburicase, the recombinant form of urate oxidase, has shown to be very effective in preventing and treating hyperuricemia. Rasburicase, in contrast with the non-recombinant form of urate oxidase uricozyme, is associated with a low incidence of hypersensitivity reactions. In addition to the demonstrated clinical benefit, rasburicase also proved to be a cost-effective option in the management of hyperuricemia.     

Uric Acid Is Independently Associated with Diabetic Kidney Disease: A Cross-Sectional Study in a Chinese Population

Background

Association between hyperuricaemia and chronic kidney disease has been studied widely, but the influence of uric acid on the kidneys remains controversial. We aimed to summarize the association between uric acid and diabetic kidney disease (DKD), and to evaluate the role of uric acid in DKD.

Methods

We enrolled 3,212 type 2 diabetic patients in a cross-sectional study. The patients’ basic characteristics (sex, age, BMI, duration of disease, and blood pressure) and chemical parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), microalbuminuria, creatinine, and uric acid) were recorded, and the association between uric acid and DKD was evaluated.

Results

In the 3,212 diabetic patients, the prevalence of diabetic kidney disease was higher in hyperuricaemic patients than in patients with normouricaemia (68.3% vs 41.5%). The prevalence of DKD increased with increasing uric acid (p <0.0001). Logistic analysis identified uric acid as an independent predictor of DKD (p <0.0001; adjusted OR (95%CI) = 1.005 (1.004–1.007), p <0.0001). Uric acid was positively correlated with albuminuria and creatinine levels (p<0.0001) but negatively correlated with eGFR (p<0.0001) after adjusting for confounding factors.

Conclusions

Hyperuricaemia is a risk factor for DKD. Serum uric acid levels within the high-normal range are independently associated with DKD.     

Adenosine in hemorrhagic shock: possible role in attenuating sympathetic activation

Changes in plasma purine nucleoside level, autonomic activity and hemodynamic reactions were studied in pentobarbital anesthetized rabbits during hemorrhagic shock. Shock was elicited by bleeding the animals to a mean blood pressure of 40 mmHg and maintained until 60% of the maximum bleeding volume in the reservoir had been taken up spontaneously. The remaining shed blood was reinfused thereafter. Norepinephrine (NE), epinephrine (E), adenosine (AD) and uric acid were measured by HPLC with electrochemical detection, fluorometry or UV absorbance. The results showed hemorrhagic shock caused a significant rise in plasma NE, E, AD, and uric acid levels, but the magnitudes and time profiles were different among them. Plasma NE and E increased during the shock compensatory period then declined in the decompensation period whereas adenosine and its metabolite uric acid were elevated persistently during both periods. It is concluded that a balance between autonomic activity and tissue metabolism is important in the maintenance of hemodynamics during shock.     

microRNA及Wnt 信号通路在急性淋巴细胞白血病中的作用研究进展

micro RNAs(mi RNAs)是一种内源性的基因调控元件,参与细胞增殖、分化、凋亡等多种重要生物学过程。在许多实体瘤和血液系统恶性肿瘤中均存在mi RNA异常表达,说明mi RNA可能参与肿瘤的发生及发展。Wnt通路是一条经典的信号通路,其异常激活与多种实体瘤和血液系统恶性肿瘤的发生发展密切相关。急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)是一种常见的成人血液系统恶性肿瘤,现已发现多种mi RNA在ALL中异常表达,并与发病、治疗效果及预后有关。在ALL中可见Wnt信号通路的异常激活及通路抑制剂的异常失活,并且这些变化与ALL的预后密切相关。本文就mi RNAs和Wnt信号通路在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)中的作用相关研究进展作一综述,以提供靶向治疗ALL的新思路。     

Application of high throughput cell array technology to FISH: investigation of the role of deletion of p16 gene in leukemias

Bio-cell chip is a chip that has hundreds of types of cells arrayed and immobilized on a small slide. To elucidate the role of deletion of the p16 gene in hematologic malignancies, the bio-cell chip technique was applied to fluorescent in situ hybridization (FISH) study. We made a bio-cell chip with bone marrow specimen from 109 patients with acute lymphoblastic leukemia (ALL), 102 patients with acute myelogenous leukemia (AML), 47 patients with chronic myelogenous leukemia (CML), and 25 patients with multiple myeloma (MM). A glass slide with 96 separated areas was fabricated, onto which was added methanol/acetic acid fixed cell suspensions for high-throughput FISH for p16. With the successful application of bio-cell chip technique, we found that the deletion of p16 contributed to the oncogenesis in acute leukemia, but not in chronic leukemia. In conclusion, the bio-cell chip, a cell version of ultrahigh-throughput technology, was successfully applied to the FISH study, which can be utilized efficiently in the molecular cytogenetic investigation of hematologic malignancies.     

2 型糖尿病合并高血压患者发生心房颤动的相关因素分析

目的:探讨2型糖尿病合并高血压住院患者发生心房颤动的相关因素。方法:选取我院收治的2型糖尿病合并高血压发生心房颤动的患者112例为研究对象(房颤组,n=112例),同期选取与房颤组年龄及性别相匹配的未发生房颤的2型糖尿病合并高血压患者150例为对照组(n=150例),比较两组患者的一般临床资料、实验室检查指标等的差异,用Logistic回归方程分析患者并发房颤的相关因素。结果:与对照组比较,房颤组患者收缩压(SBP)较高,高血压比例高、服用ACEI/ARB类药物偏低(P0.05)、左室射血分数(LVEF)偏低(P0.05)、左房内径(LAD)长(P0.05)、甘油三酯(TC)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1c)、血肌酐(Scr)、B型脑钠肽(BNP)、高敏C反应蛋白(hs-CRP)、尿酸均较高(P0.05);多因素Logistic回归方程分析提示:LAD、HbA1c、BNP、hs-CRP、尿酸是患者并发房颤的独立危险因素(P0.05),而服用ACEI/ARB类药物为保护性因素。结论:LAD、HbA1c、BNP、hs-CRP、尿酸均可能是2型糖尿病合并高血压患者发生心房颤动的独立危险因素。     

血清尿酸水平与老年轻度高血压患者的内皮功能相关性分析

目的:探讨血清尿酸水平与老年轻度高血压患者的内皮功能相关性。方法:选取我院2020年1月到2020年12月共收治的200例老年轻度高血压患者作为研究对象,所有患者均为未使用过降压药物治疗,将其分为轻度高血压组。另选取同期收治的200例高血压常规药物治疗患者作为重度高血压组与200名健康者作为对照组,对比三组患者血清尿酸水平与血管内皮功能。对观察组所有患者依照血清尿酸水平进行分组,将血清尿酸水平208-360μmol/L的患者分为低尿酸组,共计136例,将血清尿酸水平≥360μmol/L的患者分为高尿酸组,共计64例。对比两组患者的一般临床指标、血管内皮功能与氧化应激指标,并分析血清尿酸水平与老年轻度高血压患者的内皮功能相关性。结果:重度、轻度高血压组与对照组患者NO、ET-1、SUA水平对比差异显著,具有统计学意义(P<0.05);高尿酸组与低尿酸组患者TG、TC、DBP、SBP水平对比无明显差异(P>0.05),高尿酸组患者Cr水平高于低尿酸组,组间对比,差异具有统计学意义(P<0.05);高尿酸组与低尿酸组患者T-AOC、GSH-Px、LHP、MDA、NO、ET-1水平对比差异显著,高尿酸组患者LHP、MDA和ET-1水平明显高于低尿酸组,高尿酸组患者T-AOC、GSH-Px、NO水平明显低于低尿酸组,组间对比,差异具有统计学意义(P>0.05);Spearman相关分析结果显示:TG、TC、Cr、DBP、SBP与血尿酸水平无明显相关性(P>0.05),T-AOC、GSH-Px、NO与血清尿酸水平呈负相关(P<0.05),LHP、MDA、ET-1与血清尿酸水平呈正相关(P<0.05)。结论:血清尿酸水平与老年轻度高血压患者的内皮功能具有明显相关性,而且证明血尿酸水平的升高可能由患者氧化应激导致,因此氧化应激水平也是引起血管内皮功能障碍的一种潜在机制,希望本研究结果能够为高血压患者的疾病控制提供参考意见。     

Cryptococcosis in Patients with Hematologic Diseases

Purpose of Review

In this paper, we reviewed the epidemiology, diagnosis, and treatment of cryptococcosis in patients with hematologic malignancies. We reviewed all case series of cryptococcosis in different hematologic conditions, and looked at epidemiologic trends considering the new antineoplastic drugs introduced in the treatment of hematologic malignancies.

Recent Findings

Case series of cryptococcosis in patients with hematologic malignancies are scarce. We identified an increase in the proportion of cases of cryptococcosis occurring in patients with hematologic malignancies, and many case reports of cryptococcosis in patients receiving ibrutinib, a Bruton kinase inhibitor used in the treatment of chronic lymphoproliferative diseases.

Summary

Cryptococcosis is uncommon in patients with hematologic malignancies, but its occurrence may be associated with poor outcome. Hematologists should be aware of this complication if patients develop neurologic symptoms or present with pulmonary infiltrates that do not improve with antibiotics.