Revisiting intrathecal thiotepa: Efficacy and safety in secondary CNS malignancies.

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.

Complete response of mantle cell lymphoma with central nervous system involvement at diagnosis with acalabrutinib - Case report.

Central nervous system (CNS) involvement by mantle cell lymphoma (MCL) is rare and portends a poor prognosis. We describe the first patient to have a complete response with front-line treatment with single-agent acalabrutinib for MCL CNS.

Parasitic infections in hematopoietic stem cell transplant recipients.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a vital treatment for various hematological disorders. However, HSCT recipients face increased risks of infectious complications due to immunosuppression. Parasitic infections are a significant concern in this vulnerable population and can lead to substantial morbidity and mortality. This review examines parasitic infections in HSCT recipients, focusing on major infections affecting different organ systems, including intestinal parasites (Giardia spp., Entamoeba histolytica, and Cryptosporidium spp.), hematologic parasites (Plasmodium spp. and Babesia spp.), and tissue/visceral parasites (Toxoplasma gondii, Leishmania spp., and Trypanosoma cruzi). METHODS: A systematic search of relevant literature was conducted and included studies up to August 2023. Databases included PubMed, Google Scholar, were queried using specific keywords related to parasitic infections in HSCT patients. The epidemiology, risk factors, clinical presentation, diagnostic methods, and treatment approaches for each infection were evaluated. RESULTS AND CONCLUSION: Knowing the epidemiology, risk factors, and clinical presentations are crucial for timely intervention and successful management. By emphasizing early detection, effective therapies, and the unique challenges posed by each of these infections, this review highlights the importance of tailored strategies for HSCT recipients. Future research can further refine management protocols to enhance care and outcomes for these patients.

The role of androgen therapy in acquired aplastic anemia and other bone marrow failure syndromes.

Bone marrow failure syndromes are a heterogeneous group of diseases. With the major advancements in diagnostic tools and sequencing techniques, these diseases may be better classified and therapies may be further tailored. Androgens, a historic group of drugs, were found to stimulate hematopoiesis by enhancing the responsiveness of progenitors. These agents have been used for decades to treat different forms of bone marrow failure. With the availability of more effective pathways to treat BMF, androgens are less used currently. Nevertheless, this group of drugs may serve BMF patients where standard therapy is contraindicated or not available. In this article, we review the published literature addressing the use of androgens in BMF patients and we make recommendations on how to best use this class of drugs within the current therapeutic landscape.

Improved survival of adolescents and young adults patients with T-cell acute lymphoblastic leukemia.

Aim: The outcome of T-cell acute lymphoblastic leukemia (T-ALL) has improved with the use of pediatric-inspired protocols in the adolescents and young adults (AYA) population. There is limited literature regarding the outcome of T-ALL/lymphoblastic lymphoma (LBL) AYA patients treated with pediatric protocols. Methods: A total of 35 T-ALL/LBL-AYA patients ages between 14 and 55 years were treated with AYA-15 protocol. Results: At a median follow-up of 5 years the overall survival, disease-free survival and event-free survival are 71%, 62% and 49.6% respectively. Toxicities were within the expected range. Conclusion: Our single-center experience real-world data in treating T-ALL/LBL-AYA patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

Pediatric-type follicular lymphoma: a short review.

Pediatric-type follicular lymphoma is an uncommon and newly recognized entity of lymphoid neoplasm commonly encountered in the young population. Despite its indolent clinical course and localized nodal involvement, it has been characterized by its high-grade histopathological features. The overlapping features between this disease and several entities have made approaching this unique entity significantly challenging, with all such features being reflected in the strict diagnostic criteria highlighted by the WHO 2016 lymphoid malignancy classification. Despite its characteristic high-grade histology, its cure rates have remained high, with relapse and transformation rarely occurring. Interestingly, several cases have achieved remission following nodal disease resection, possibly eliminating the need for chemotherapy and radiation and preventing long-term morbidities from later approaches in disease survivors.

Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade.

AIM: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. METHODS: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts' suggestions. RESULTS: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. DISCUSSION: The inconsistency of the results in the literature can be attributed to the studies' small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. CONCLUSION: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.

Worldwide Network for Blood and Marrow Transplantation Special Article on Key Elements in Quality and Accreditation in Hematopoietic Stem Cell Transplantation and Cellular Therapy.

Hematopoietic stem cell transplantation (HSCT) represents an example of a highly complex and costly medical procedure with major applications in hematology and oncology. It is associated with life-threatening complications and, consequently, increased demands on healthcare resources. Although improving quality is an integral component of healthcare strategic planning, drivers of quality may be variable, and there is logical debate as to what drives quality in HSCT. Moreover, HSCT programs differ in structure and availability of resources, which drive the type of transplantations provided and determine what is affordable and/or economically feasible. The complexity of HSCT procedures with involvement of different stakeholders necessitates not only regulatory frameworks, but also robust quality systems to ensure consistent standards, demonstrate transparency for regulators, and define what quality means within the HSCT program. In an era of escalating healthcare complexity and heightened fiscal responsibility, transparency and accountability, accreditation contributes to ensuring that care meets the highest standards and can serve as a risk mitigation strategy. Quality management has become an indispensable tool for the management of a complex medical intervention such as HSCT. It allows the transplantation team to monitor its activities and identify areas for continuous improvement. The Worldwide Network for Blood and Marrow Transplantation invited a group of international experts in HSCT and quality management to work on providing a summary document about the key elements in quality and accreditation in HSCT and highlight the foremost challenges of implementing them, with a special focus on low- and middle-income economies.

Upfront Alternative Donor Transplant versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack a Fully HLA-Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies, on Behalf of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Improved survival in adolescents and young adults (AYA) patients aged 14-55 years with acute lymphoblastic leukemia using pediatric-inspired protocol - a retrospective analysis of a real-world experience in 79 of patients treated at a national tertiary care referral center.

BACKGROUND: Treating adolescents and young adults (AYA) patients with acute lymphoblastic leukemia (ALL) using pediatric-inspired protocols have shown improvement in outcomes. Most data available in the literature of such protocols is derived from well-controlled clinical trials. This report aims to provide a real-world experience from using a pediatric-inspired protocol in ALL-AYA population in larger number of patients treated at a national tertiary care referral center. METHODS: Newly diagnosed Philadelphia negative ALL-AYA patients ages between 14 and 55 years of age were treated on an institutional protocol (AYA-15 protocol) adopted from a modified version of Children's Cancer Group (CCG) 1900 protocol. At the time of this publication, a total of 79 patients were treated using the AYA-15 protocol between 2015 and 2020). Event-free survival (FFS), disease-free survival (DFS), and overall survival (OS) were analyzed using cumulative incidence and Kaplan-Meier methods. RESULTS: The median age at diagnosis was 18 years (14-51 years) with 63% male patients. Complete remission (CR) at day 28 of induction was achieved in 88.6% of which 73.4% were minimal residual disease (MRD) negative. At a median follow up of 5 years, EFS, DFS and OS were 57.5%, 69.2% and 75.8% respectively. Toxicities were within the expected range with infections and transaminitis being the most common adverse events. CONCLUSION: Our single-center experience real-world data in treating AYA-ALL patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

Outcomes of autologous stem cell transplantation for multiple myeloma in Saudi Arabia.

BACKGROUND: In 2015, multiple myeloma (MM) represented 1% of all cancers and about 5% of hematologic malignancies in Saudi cancer registry. We conducted this large study because only small pilot studies have examined MM outcomes after autologous stem-cell transplantation (ASCT). The standard therapy for eligible patients is induction chemotherapy followed by ASCT. OBJECTIVES: Determine the demographic characteristics of MM patients and the outcomes of ASCT. DESIGN: Retrospective. SETTING: Tumor registry database of major tertiary cancer care center in Riyadh. PATIENTS AND METHODS: We identified patients with newly diagnosed MM who underwent ASCT from October 1997 to March 2015. MAIN OUTCOME MEASURES: The demographic characteristics of MM patients and the outcomes of ASCT in the form of response evaluation, progression-free survival (PFS) and overall survival (OS). SAMPLE SIZE: 169 patients with newly diagnosed MM. RESULTS: The median age at diagnosis was 51 years (range 23-69) and 100 (59.2%) were male. The most common immunoglobulin (Ig) subtype was IgG-kappa (80 patients; 47.6%). Most patients presented with advanced ISS stage III (75 patients; 47.5%). The cytogenetic analysis was documented in only 87 patients (51.4%); about half (48.3%) had normal cytogenetics by fluorescence in situ hybridization. Deletion 13 was present in 18.4% of patients. In post-induction therapy, 84 patients (50%) achieved a complete response, which increased to 78.1% (132 patients) after ASCT. The median PFS and OS post-transplantation were 30 and 202 months, respectively. Only one patient (<1%) died in the first 100 days after transplantation. CONCLUSIONS: Our transplant eligible MM patients tend to be younger with a higher OS and a low ASCT-related mortality (<1%) than is reported internationally. LIMITATIONS: Usual limitations of a retrospective analysis using registry-level data; no data on quality of life. CONFLICTS OF INTEREST: None.

The outcomes of secondary AML post allogeneic hematopoietic cell transplantation significantly depend on the presence of poor-risk cytogenetic abnormalities.

Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy-related AML. Large registry-based data identified sAML as an independent poor-outcome type of AML post allogeneic hematopoietic cell transplantation (allo-HCT). In our study, we tried to define factors affecting outcomes of sAML post allo-HCT, and identify patients with sAML who may truly benefit from allo-HCT. We retrospectively analyzed the data of 64 patients aged (14-61 years) with sAML who received allo-HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor-risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease-free survival (DFS; P-value = .009, and .004, respectively). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was significantly lower in sAML patients with poor-risk cytogenetics (P-value = .003) resulting in a high risk of death without cGVHD in this group of patients (P-value = .02). Besides, GVHD relapse-free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II-IV cGVHD in the first 2 years post allo-HCT. We conclude that sAML patients with poor-risk cytogenetics have a significantly lower DFS post allo-HCT with a high risk of death without active cGVHD.