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Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production resulting in elevated hemoglobin and/or hematocrit levels. Patients often have symptoms such as fatigue, pruritus, and painful splenomegaly, but are also at risk of thrombosis, both venous and arterial. Ruxolitinib, a selective Janus kinase inhibitor, is approved by the US Food and Drug Administration as second-line cytoreductive treatment after intolerance or inadequate response to hydroxyurea. Although ruxolitinib has been widely used in this setting, limited data exist in the literature on ruxolitinib treatment patterns and outcomes among patients with PV in routine clinical practice. We report a retrospective, observational, cohort study of patients treated for PV with ruxolitinib across three US centers (academic and regional practice) from December 2014-December 2019. The study included 69 patients, with a median follow-up duration of 3.7 years (95% CI, 2.9-4.4). Our data demonstrate very high rates of hematocrit control (88% of patients by three months and 89% by six months); few patients required dose adjustments or suspension. No arterial thromboses were observed; however, the follow-up duration does not allow for the generation of meaningful conclusions from this. Three patients had thrombotic events; one was in the setting of a second malignancy, one post-operative, and a third related to prolonged immobility. We also found that 28% of patients initiated ruxolitinib as a result of poorly controlled platelet counts, second only to hydroxyurea intolerance (46%) as a reason to start therapy. In clinical practice, ruxolitinib continues to be effective in controlling hematocrit levels after three and six months of treatment in patients and is associated with low thrombotic risk., (© 2024. The Author(s).)

Purpose: Patients with hematologic malignancies are extremely vulnerable to financial toxicity (FT) because of the high costs of treatment and health care utilization. This pilot study identified patients at high risk because of FT and attempted to improve clinical outcomes with comprehensive intervention., Methods: All patients who presented to the Levine Cancer Institute's Leukemia Clinic between May 26, 2019, and March 10, 2020, were screened for inclusion by standardized two question previsit survey. Patients screening positive were enrolled in the comprehensive intervention that used nurse navigators, clinical pharmacists, and community pro bono financial planners. Primary outcomes were defined as improvement in mental and physical quality of life in all patients and improvement in overall survival in the high-risk disease group., Results: One hundred seven patients completed comprehensive intervention. Patients experiencing FT had increased rates of noncompliance including to prescription (16.8%) and over-the-counter medications (15.9%). The intervention resulted in statistically significantly higher quality of life when measured by using Patient-Reported Outcomes Measurement Information System physical (12.5 ± 2.2 v 13.7 ± 1.8) and mental health scores (11.4 ± 2.2 v 12.4 ± 2.2; all P < .001). In patients with high-risk disease (as determined by using disease-specific scoring systems), risk of death in those receiving the intervention was 0.44 times the risk of death in those without the intervention after adjusting for race, and treatment with stem-cell transplant, oral chemotherapy, or immunotherapy (95% CI, 0.21 to 0.94; P = .034)., Conclusion: Screening and intervention on FT for patients with hematologic malignancies is associated with increased quality of life and survival.

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms., (© 2021 Wiley Periodicals LLC.)

Hemorrhagic cystitis (HC) is a common and important complication of allogeneic hematopoietic cell transplantation (HCT). Reactivation of BK virus is its most common cause. The more intense immunosuppressive regimens administered to recipients of grafts from alternative donors have been reported to account for the increased susceptibility to HC in this population. This study compares patients undergoing HCT with either a haploidentical donor or a matched related donor, all of whom received identical immunosuppression with a post-transplantation cyclophosphamide-based regimen. The incidence of HC was significantly higher in the patients receiving a haploidentical graft (P = .01). The higher incidence of HC in haploidentical graft recipients is therefore directly related to the inherent immune deficiency that follows HLA-mismatched transplantation, independent of the intensity of pharmacologic immunosuppression. This finding carries significant clinical impact for the prevention and treatment of HC in haploidentical graft recipients., (Copyright © 2019. Published by Elsevier Inc.)

Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments. While selection of initial treatment was dictated by clinical features, the initial responses, as well as overall responses to methotrexate (MTX), cyclosporine (CsA), and cyclophosphamide (CTX), were similar at 40-50% across drugs. Sequential use of these drugs resulted in responses in most cases: only 10-20% required salvage therapies such as ATG, Campath, tofacitinib, splenectomy or abatacept. MTX yielded the most durable responses. STAT3-mutated patients required therapy more frequently and had better overall survival.

Myelodysplastic syndrome (MDS) is a heterogeneous group of malignant disorders of blood cell production occurring predominantly in elderly patients. While low intensity treatments are appropriate initially in most patients with favorable prognoses, hematopoietic cell transplantation (HCT) is the only curative therapy and is the best therapy for many higher risk patients. In patients who present with lower-risk disease, HCT may be considered at the time of meaningful disease progression. In patients receiving hypomethylating treatment, outcome of HCT is best when performed during response, and HCT is less effective when performed after resistance occurs. Advances over the last 2 decades have markedly improved safety and survival with HCT, and appropriate donors are now available for virtually every patient in whom HCT is indicated. The application of HCT in MDS has expanded significantly over the last few years and its use in MDS promises to continue to grow as results further improve.

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.

Pain management at the emergency department (ED) for vaso-occulsive crisis (VOC) for patients with sickle cell disease has not been optimum, with a long delay in giving the initial analgesic. We conducted a retrospective survey over a 7-year period to determine our ED's timing in giving pain medication to patients with VOC as a quality improvement project. We compared different periods, children vs adults, and the influence of gender in the analgesic administration timing. This is a retrospective chart review of three different periods: (1) years 2007-2008, (2) years 2011-2012, and (3) year 2013. We extracted relevant information from ED records. Data were analyzed using Student t test, chi-square analysis, and the Kruskal-Wallis test. There was a progressive improvement in the time interval to the 1st analgesic over these three periods. Children received analgesics more quickly than adults in all periods. Male adult patients received pain medication faster than female adult patients, although initial pain scores were higher in female than in male patients. Progressively fewer pediatric patients utilized ED over these three periods, but no difference for adult patients was observed. The proportion of pediatric patients admitted to the hospital increased with each period. The progressive decrease in both the number of patients and the number of visits to the ED by children suggested that the collective number of VOC in children has decreased, possibly secondary to the dissemination of hydroxyurea use. We failed to observe the same trend in adult patients. The need for IV access, and ordering laboratory tests or imaging studies tends to delay analgesic administration. Delay in administration of the first analgesic was more pronounced for female adult patients than male adult patients in spite of their higher pain score. Health care providers working in ED should make conscious efforts to respect pain in women as well as pain in men. Though not proven from this study, we believe that a significantly wider use of hydroxyurea by adult patients most likely would reduce their utilization of ED for the purpose of relief of pain, and further pediatric hematologists may be better positioned to increase hydroxyurea adherence by young adult patients, since they have had established rapport with them before transitioning to adult care.

Purpose: To present the safety and short-term outcomes of using controlled blunt microdissection catheter-assisted revascularization of symptomatic chronic total occlusions of the lower extremity., Materials and Methods: A retrospective study was performed on 61 patients (46 men) with a mean age of 72.3 years +/- 9.4 who underwent 67 procedures in 86 arteries between June 2003 and March 2007 for claudication (38 procedures, 57%), rest pain (19 procedures, 28%), and tissue loss (10 procedures, 15%). Technical success was defined as successful traversal of the occlusion. Duplex ultrasonography (US) was used to assess patency. Clinical patency was defined as at least one category improvement in Rutherford score from baseline and absence of target limb revascularization or major amputation at 6 months., Results: Chronic total occlusions were located in aortoiliac (11 arteries, 13%), infrainguinal (72 arteries, 83%), and infrapopliteal (four arteries, 5%) arteries. The mean lesion length was 14.2 cm +/- 8. The tibial run-off vessels was 1.9 vessels +/- 0.8. The technical success rate of the procedure was 84%. Advanced age (P = .04), renal function (P = .02), and target lesion length (P < or = .01) were predictors of technical failure. The clinical success rate at 6 months was 92%, and the primary patency with duplex US was 87%. Renal function (P < or = .01), length of the occlusion (P < or =.01), number of stents per procedure (P < or =.01), and tibial run-off vessels (P = .05) were the predictors of clinical success., Conclusions: The controlled blunt microdissection catheter is safe in the revascularization of chronic total occlusions of the lower extremity. The technical success rate was 84% and predicted by age, renal function, and lesion characteristics. Clinical patency at 6 months was 92% and predicted by renal function, lesion characteristics, and run-off.

Purpose: The purpose of the present study was to report safety, efficacy, and renal function outcomes with use of the GuardWire embolic protection device (EPD) in renal artery stent placement for patients with renal artery stenosis (RAS) and chronic renal insufficiency (CRI)., Materials and Methods: This was a retrospective study of all patients with RAS and CRI treated concomitantly with a GuardWire EPD and renal artery stents from December 2002 through June 2006. Renal function was determined by calculating the estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease formula, and subjects were divided into Kidney Disease Outcomes and Quality Initiative (K-DOQI) classes based on baseline eGFR. After revascularization, an improvement from baseline of at least one K-DOQI class was defined as improvement, unchanged K-DOQI class as stabilization, and worsening of at least one K-DOQI class as deterioration., Results: There were 63 patients (54% men) with a mean age of 75.2 years +/- 7.7. The mean baseline serum creatinine level and eGFR were 1.87 mg/dL +/- 0.6 (range, 1-3.8 mg/dL) and 36.63 mL/min per 1.73 m(2) +/- 11.42 (range, 13.85-59.99 mL/min per 1.73 m(2)), respectively, and at the last clinical follow-up, the respective measurements were 1.96 mg/dL +/- 0.72 and 38.75 mL/min per 1.73 m(2) +/- 13.25 (P = not significant). Over a mean follow-up period of 16 months +/- 12, 14 patients (25%) showed improvement, 33 (58%) had stable renal function, and 10 (18%) showed deterioration. There was one GuardWire-related dissection, which was successfully treated with a stent., Conclusions: The GuardWire EPD, used during renal artery stent placement, is safe and was associated with stabilization or improvement in kidney function in 83% of patients with RAS and CRI.