Management Of Hematologic Diseases Research Articles

The role of the pulmonary function laboratory in the management of hematologic diseases

The role of the pulmonary function laboratory in the management of hematologic diseases

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Simulation-based Bone Marrow Aspiration and Trephine Biopsy Education for Medical Students: A Non-randomized Controlled Trial.

Introduction Despite the critical role of bone marrow aspiration and a trephine biopsy (BMAT) in the diagnosis and management of hematological diseases, research on effective teaching methods is limited. Medical students traditionally learn to perform BMAT through observation and replication, which poses a risk to patient safety. Therefore, we developed a novel BMAT simulator for undergraduate medical students using a simulation-based education program. Methods This program, designed for fourth- and fifth-year medical students at Okayama University Medical School, included pre-study materials and one hour of simulation training. Internists practicing hematology served as the controls. Before and after the simulation training, the students completed questionnaires regarding self-confidence, self-evaluation, interest, and knowledge. The procedures were evaluated objectively using a checklist at the end of the program. Results There were significant improvements in self-evaluation, self-confidence, interest, and knowledge acquisition after the simulation program (p≤0.001). The checklist revealed that the mean overall proficiency level of the students was 76.9%, which was significantly higher than that of internists (63.5%) (p≤0.01). Conclusion Our simulation-based education program using the novel BMAT simulator improved medical students' BMAT knowledge and skills.

Impact on mental health, disease management, and socioeconomic modifications in hematological patients during the COVID-19 pandemic in Italy.

Hematological patients are a highly vulnerable population with an increased risk of developing severe COVID-19 symptoms due to their immunocompromised status. COVID-19 has proven to cause serious mental health issues, such as stress, anxiety, and depression in the general population. However, data on the psycho-social impact of COVID-19 on hematological patients are lacking. This study aims to examine the psychological well-being of hematological patients in Italy during the initial period of the COVID-19 pandemic. Furthermore, it seeks to explore the association between modifications in the management of hematological diseases and employment status of these patients during the COVID-19 pandemic and the resulting mental health outcomes. A survey using the DASS-21 questionnaire was administered to 1105 hematological patients. Data analysis was conducted using the R software, and logistic regression analysis was performed to predict the association between hematological patient/general population and employment status with DASS scores. The hematological patient population reported significantly higher levels of depression (OR 0.947, 95% CI 0.966-0.982, p < 0.001), anxiety (OR 0.948, 95% CI 0.939-0.958, p < 0.001), and stress (OR 0.984, 95% CI 0.977-0.992, p < 0.001) compared with the general population. A significant relationship has been found in stress between employed and unemployed patients (OR 1.015, 95% CI 1.000-1.030, p = 0.044), as well as in the control group (OR 1.024, 95% CI 1.010-1.039, p = 0.001). In addition, employment status is significantly related to depression, anxiety, and stress in both the hematological patient group and the general population. During the initial phase of the COVID-19 pandemic, hematological patients had elevated levels of depression, anxiety, and stress compared with the general population. The delay in their treatment and employment status played a role in their mental health outcomes. These findings emphasize the importance of further research to gain deeper insight into the long-term psychological effects and explore effective strategies for managing mental health in similar crises.

Systematic Review of Infectious Events in Prospective Trials of Ibrutinib

Systematic review of infectious events in prospective trials of IbrutinibIbrutinib is an oral small molecule inhibitor of Bruton tyrosine kinase (BTK). It is efficacious in the treatment of multiple B cell lineage disorders including chronic lymphocytic leukemia, mantle cell lymphoma and Waldenström macroglobulinemia. Use is expanding with ongoing clinical trials in solid tumor oncology as well as recent FDA approval for the treatment of chronic graft versus host disease (GVHD). As experience with newer targeted agents increases we are developing better appreciation and recognition of sometimes unanticipated toxicities. While the most common side effects with ibrutinib are rash and diarrhea, signals of concern have been seen with adverse effects related to hemorrhage, pneumonitis and recent attention to cardiac arrhythmias. Based on our own institutional experience, we updated a preliminary systematic review of infectious events in prospective trials of ibrutinib in the treatment of hematologic disorders.We reviewed the published literature and major conference abstracts using PubMed, Google Scholar and HemOnc.org. Publications through July 1, 2017 were included in the evaluation. All prospective trials of ibrutinib for the treatment of hematologic malignancies were included in the analysis. Those trials involving solid oncologic tumors, GVHD or following allogeneic stem cell transplant were excluded. Infectious events included pneumonia, sepsis, genitourinary and respiratory tract infections, sinusitis, cellulitis, infectious colitis or febrile neutropenia. Neutropenia without fever as well as inflammatory conditions (e.g., pneumonitis) without mention of infection were not included. Pneumonia was separately annotated and included bacterial, fungal, viral or other atypical causes if identified. Events were grouped by grade according to the Common Terminology Criteria for Adverse Events, version 4.03. In multi-arm trials only the ibrutinib-containing arms were included in the analysis and we generally restricted this on an intention-to-treat basis.From the updated literature review, 929 publications from PubMed, 772 from meeting abstracts and more than 11,000 from Google Scholar were identified. 33 peer reviewed publications and 106 abstracts reporting on 61 trials including more than 2300 patients were identified.Infectious adverse events of any grade were identified in over half of the patients for which data was available. Additionally, pneumonia accounted for half of the grade 3/4 infectious events and there were 33 grade 5 pneumonias identified among the studies. A number of significant infectious events were attributed to atypical organisms such as Aspergillus spp., Cryptococcus neoformans and Pneumocystis jirovecii . Somewhat counterintuitively, the rates of all events (infections, pneumonia or any grade 5 event) were consistently lower in the studies involving combination regimens. This finding may represent a gap in the data as many of these trials are incomplete and many are only reported in abstract format at the time of this analysis. Alternatively, this may be due to a more heavily pretreated population with relatively diminished performance status enrolled in the single agent trials.Among all studies grade 3/4 pneumonia was seen in 13% of patients on ibrutinib alone and 7.8% of patients on combination therapy. Grade 5 infections accounted for 25-33% of all grade 5 events. With increasing use of targeted therapies in patients previously not eligible for standard cytotoxic regimens, clinicians must be aware of unanticipated side effects. In one trial with a high rate of invasive aspergillosis, there was no correlation between patient CD4+ T cell counts and rates of this opportunistic infection. A separate investigation identified high rates of P. jirovecii in patients on single agent ibrutinib. Inhibition of BTK in non-malignant monocytes has been a proposed mechanism of increased susceptibility to invasive fungal disease. Antimicrobial prophylaxis with ibrutinib use is not currently standard practice in the management of hematologic diseases. Our findings of high rates of infectious events, particularly pneumonia often related to opportunistic pathogens, suggest that vigilance for infection is mandatory, and that risk factors for predisposition to infection, beyond CD4+ T cell counts and immunoglobulin levels, should be sought. [Display omitted] DisclosuresPauff:Abbvie: Employment.

Laparoscopic versus open Splenectomy in the management of hematological diseases

Laparoscopic versus open Splenectomy in the management of hematological diseases

Azacytidine Inhibits Megakaryopoiesis Via the Induction of Immunogenic RNA Species and Activation of Type-I Interferon Signaling

Management of hematologic disease- and therapy-related thrombocytopenia remains a serious clinical issue, especially in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The ribonucleoside and DNA-demethylating agent azacytidine (AZA), has proven useful for the treatment of patients with MDS and AML not eligible for stem cell transplantation. While low-dose AZA therapy induces clinical remissions in up to 50% of treated patients, it comes at the cost of aggravating pre-existing thrombocytopenia which is observed in a subset of patients; this can lead to increased bleeding and bleeding-associated mortality, and importantly, often requires dose modifications and delays of therapy. Thus, identification of strategies alleviating ineffective megakaryopoiesis will likely lead to increased therapeutic efficacy for patients with MDS/AML. Eltrombopag (EP), a second-generation small molecule thrombopoietin receptor (TPO-R) agonist was effective in raising platelet counts in patients with MDS as a single agent, as well as in combination with certain standard of care therapies. However, it failed to stimulate platelet production during the first four cycles of AZA treatment as uncovered by a recent phase III placebo-controlled clinical study (SUPPORT; NCT02158936). The goals of this study were to identify the cellular and molecular underpinnings of AZA-associated inhibition of megakaryopoiesis and to assess the ineffectiveness of EP in mitigating AZA treatment-associated thrombocytopenia. Our results demonstrate that at a clinically-equivalent and non-cytotoxic dose, AZA rapidly induces transient activation of interferon type I (IFN-I) signaling in various hematopoietic cell types, including stem and lineage-committed progenitor cells (HSPCs). We detected IFNα and IFNβ production and release using ELISA and intracellular flow cytometry on primary total mononuclear cell- and purified CD34-positive HSPC populations derived from cord blood, bone marrow from healthy volunteers or patients with MDS/AML. AZA-mediated activation of Type I IFNs in healthy control- and MDS/AML cells was preceded by an accumulation of double-stranded RNA (dsRNA) species and decreased total RNA cytosine methylation measured by immunocytochemistry and intracellular FACS analysis; this suggested that AZA triggered the accumulation of immunogenic RNA species which elicit an IFN-I response. In support, we found Toll like receptor 3 (TLR3) activation and phosphorylation of STAT1 in CD34+ HPSC, along with premature activation of Suppressor of Cytokine Signaling 1 (SOCS1), a well-known JAK/STAT-dependent signaling attenuator. This rapid AZA-induced viral mimicry response led to abrogation of thrombopoietin (TPO) or EP-stimulated TPO-R signaling and inhibition of ex vivo megakaryocyte progenitor proliferation quantified by colony formation in semi-solid medium. Importantly, inhibition of IFN-I signal activation using the JAK3 inhibitor decernotinib, the IFNα/β-blocking peptide, B18R, or RNA interference-mediated knock-down of SOCS1 counteracted the inhibitory effects of AZA on TPO-R stimulation and restored megakaryopoiesis. Given these observations, we pre-clinically tested a revised treatment protocol, in which primary cells were first exposed to AZA for four days followed by TPO-R stimulation using TPO or EP. This new treatment strategy alleviated AZA's inhibitory effects at the molecular and cellular levels, demonstrating that upon resolution of the AZA-mediated vial mimicry response, EP and TPO can effectively stimulate TPO-R signaling and megakaryopoiesis. Together, our data reveal a mechanistic basis of AZA-mediated inhibition of megakaryopoiesis in patients with MDS/AML. Additionally, we show that EP cannot overcome the megakaryopoiesis-inhibitory effects of acute IFN-I signaling activation upon AZA exposure. Findings of our study are consistent with and provide a molecular explanation for the observations made in the context of the SUPPORT study. In the future, it will be critical to better understand and potentially counteract the megakaryopoiesis-inhibitory effects by IFN-I pathway activation upon AZA therapy in patients with MDS/AML. Disclosures Okoye-Okafor: Novartis Pharmaceuticals: Research Funding. Pallaud:Novartis Pharmaceuticals: Employment. Marques Ramos:Novartis Pharmaceuticals: Employment. Verma:Janssen: Research Funding; BMS: Research Funding; Celgene: Honoraria; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria. Heckman:Celgene: Research Funding; Novartis: Research Funding; Oncopeptides: Research Funding; Orion Pharma: Research Funding. Will:Novartis Pharmaceuticals: Research Funding.

General Gastroenterological Surgery: Spleen.

General Gastroenterological Surgery: Spleen.

Antifungal Drugs in the Management of Hematological Diseases in a Home Care Program

Antifungal drugs are frequently used in hematology due to relatively high frequency of infections. Electronic health records of home care patients were retrospectively scanned, looking for antifungal drugs, nystatin, fluconazole, amphotericin B, caspofungin, itraconazole, voriconazole, and posaconazole; we extrapolated frequency, type, indication for use, and duration of each identified antifungal treatment. From September 15, 2011 to September 15, 2012, among 106 patients, median age 83 years, affected by cancer in 82 and other diagnosis in 24 patients, 18 were treated with antifungals, 12 with systemic antifungal (fluconazole 6, itraconazole 5, sequential voriconazole, and itraconazole 1) and 6 with local antifungal. According to our results, the use of antifungals in home care hematological patients is frequent, but limited to certain molecules.

Laparoscopic splenectomy in the management of hematological diseases

After being successfully applied to other intraabdominal organs, the laparoscopic approach has been applied to the spleen since 1991. The experience with 17 cases of laparoscopic splenectomy performed due to immune thrombocytopenia purpura (10 instances), hereditary spherocytosis (2 cases), and Hodgkin's disease where the staging was done according to Standford (5 cases), have been reported. With the patient in anti-Trendelenburg position, and the surgeon between the patient's legs, four or five trocars are introduced into the upper abdominal quadrants and the spleen hilum is isolated. Hilar vessels are dissected and ligated with a surgical stapler. A plastic bag is introduced into the abdomen cavity and the spleen is slipped inside; it is then extracted through an umbilical incision after morcellation. Advantages of the open operation include a decrease in postoperative pain, a decrease in pulmonary sequelae, a reduced incidence of subphnic abscesses, and cosmetic advantages. The decrease of postoperative sequelae reduces hospitalization and costs, which are higher for the operation itself (materials and staff's training).

Laparoscopic splenectomy in the management of hematological diseases Surgical technique and outcome of 17 patients

Laparoscopic splenectomy in the management of hematological diseases Surgical technique and outcome of 17 patients

Elective Laparoscopic Splenectomy: Personal Experience and Literature Review

Laparoscopic splenectomy has become an attractive treatment for patients with selected hematologic disorders. Almost 200 observations have been reported. The rate of conversion to laparotomy is 10% to 15%, and the complication rate is between 0% and 30%. Adequate selection of patients, preoperative administration of intravenous immunoglobulin in patients with idiopathic thrombocytopenic purpura, meticulous surgical technique, and careful preoperative and intraoperative search for accessory spleen are critical factors for success in these patients. The procedure should be confined to expert laparoscopic surgeons with considerable experience in the management of hematologic diseases.

Granulocyte Transfusion—A Review

Advances in component transfusion therapy over the last two decades have improved the management of hematologic diseases. In patients undergoing chemotherapy for leukemia, hemorrhagic problems have been minimized with platelet transfusions. However, infectious complications due to severe granulocytopenia have surfaced as the leading cause of death in these patients. This finding stimulated vigorous research in the use of granulocytes for transfusion, resulting in progress in granulocyte collection, short-term liquid storage and clinical use. The effectiveness of granulocyte concentrates in the management of infections in severely neutropenic patients (fewer than 500 neutrophils per μl]) with documented bacterial sepsis has been amply demonstrated. Serious untoward reactions to granulocyte transfusions have been relatively rare. Some areas of granulocyte transfusion that require further investigation are 1) more precise definition of criteria for the selection of patients most likely to benefit; 2) improvements in efficiency of collection and preservation; and 3) better understanding of immunologic factors affecting efficacy of therapy.

Clinical Hematology, ed. 6, by Dr. Maxwell M. Wintrobe. Philadelphia: Lea and Febiger, 1967, 1287 pp., $22.50

The sixth edition of Wintrobe's Clinical Hematology, as all of the preceding editions, remains the "bible" of this specialty. The book reflects the author's more than 30 years of clinical preeminence and so has great practical value in the management of hematologic diseases. It also presents so definitive an evaluation of the literature that it can serve as a prime reference for the physiologic and pathologic mechanisms underlying hematologic disorders. Despite its general excellence, there are references from earlier editions which could have been eliminated.