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Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation. The primary endpoint was the comparison of survival 2 years after biologic assignment between treatment arms. Power calculations required 60 participants on the Donor Arm and 140 on the No Donor Arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives compared changes in SCD-related events, functional outcomes, and organ function. Data were analyzed by the intent-to-treat principle. A total of 113 participants were enrolled, 28 on the Donor and 85 on the No Donor Arm The 2-year probabilities of survival were 89% and 93%, on the Donor and No Donor Arms, respectively. Vaso-occlusive pain (VOC) was less frequent on the Donor Arm in the second year after biologic assignment (p < 0.001). On PROMIS-57 surveys there was decreased fatigue (p=0.003) and an increased ability to participate in social roles and activities (p=0.003) on the Donor Arm 2-years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the Donor Arm led to improvements in VOC, fatigue, and social function., (Copyright © 2024 American Society of Hematology.)

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT's efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 10 6 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.

Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real-world data published on HMAs plus VEN have been either single-center studies or using community-based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real-world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85-13.5), with OS significantly worse among patients with TP53-mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30-day and 60-day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE-A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Treatment of acute leukemia has been delivered predominantly in academic and larger leukemia treatment centers with the infrastructure and staff needed to manage patients receiving complex therapeutic regimens and supportive care. However, in recent years, several oral agents and less-myelosuppressive regimens were approved, making it possible for these patients to receive therapy in smaller community hospitals and oncology office practices. In this review, we discuss the optimum community setting, type of patient who can be treated, agents that can be applied, and an appropriate clinical circumstance in which a referral to a tertiary center should be made., Competing Interests: Conflict-of-interest disclosure: A.P.J. declares no conflicts of interest. J.E.C. consults with or has an advisory role with Amphivena Therapeutics, Astellas Pharma, Bio-Path Holdings Inc., BiolineRx, Bristol-Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer,Takeda, and received research funding from Astellas Pharma (Inst), Bristol-Myers Squibb (Inst), Daiichi Sankyo (Inst), Immunogen (Inst), Jazz Pharmaceuticals (Inst), Merus (Inst), Novartis (Inst), Pfizer (Inst), Sun Pharma (Inst), Takeda (Inst), Tolero Pharmaceuticals (Inst), and Trovagene (Inst). V.K.K. has provided consultancy or in an advisory board role for Novartis and Pfizer., (© 2020 by The American Society of Hematology.)

We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4-190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third ( n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1-53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.

BACKGROUND Essential thrombocythemia (ET) is one of the BCR-ABL gene fusion negative chronic myeloproliferative disorders (MPDs), which also include polycythemia vera (PV), and myelofibrosis. Few clinical cases have reported the progression of ET to chronic myelogenous leukemia (CML) with the expression of the BCR-ABL gene. This report describes such a case and includes a review of other reported cases of CML co-occurring with BCR-ABL-negative chronic MPDs. CASE REPORT A 49-year-old woman was diagnosed with ET in 2007. Cytogenetic testing was negative for expression of the JAK2 or BCR-ABL1 genes. Eight years later, in January 2015, she presented with excessive fatigue, poor appetite, unintentional weight loss, a white blood cell (WBC) count of 24,700 per mL, hemoglobin of 9.9 g/dl, and a platelet count of 557,000 per mL, with blasts and basophils in the blood film. Cytogenetic analysis with fluorescent in situ hybridization (FISH) confirmed a 9: 22 chromosomal translocation (Philadelphia chromosome), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression of the BCR-ABL gene, confirming a diagnosis of CML. In February 2015, first-line therapy commenced with nilotinib, which was changed to imatinib after three months. During the following nine months, qRT-PCR confirmed a trend to deep molecular remission (MR5). However, she developed early myelofibrosis, and myelosuppressive therapy was resumed. CONCLUSIONS This rare case highlights the importance of cytogenetic testing in cases of CMPD that transform to CML, not only to confirm the diagnosis but to plan treatment, as Philadelphia chromosome-positive and -negative cases differ in their management.

Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy. In 2017, the BFORE trial demonstrated efficacy of bosutinib as first-line treatment in adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The most common adverse events (AEs) of any grade in bosutinib-treated patients in BFORE were diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase, and increased aspartate aminotransferase, consistent with the most commonly reported AEs in earlier studies. To balance the efficacy and tolerability of treatment to optimize patient adherence with medications, treating physicians commonly use various strategies such as initiating treatment at a lower dose, dose reduction, or dose interruption, depending on the type and severity of the AEs and the clinical setting. In light of the recent data from first-line treatment, an expert panel of hematologists reviewed management strategies for the use of bosutinib in treatment of CP-CML and made the recommendations reported here. Although the panel focused on first-line treatment, the principles can be for the most part extended to bosutinib use in later lines of treatment. Recommendations include advice regarding prophylaxis and management for diarrhea. The panel also considered optimum timing for referral to a specialist for specific AEs. Across the commonly occurring AEs, the panel highlighted the importance of education and communication with patients about anticipated AEs.

BACKGROUND Tamiflu (oseltamivir phosphate) serves as prophylaxis and treatment of upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) caused by viruses of the Orthomyxovirus family. Here, we present a patient with URTI and negative rapid influenza diagnostic testing (RIDT), who developed rhabdomyolysis after being started on oseltamivir. CASE REPORT Our report describes a rare case of rhabdomyolysis after oseltamivir administration in a 53-year-old man with suspected influenza. We discuss the differential diagnosis for rhabdomyolysis to rule out other causes and review the literature on influenza-induced rhabdomyolysis. CONCLUSIONS Considering the serious consequences of rhabdomyolysis, care needs to be taken in routine prescription and use of oseltamivir. Although this is a rare adverse effect, our case highlights the need to be vigilant for uncommon adverse events with commonly used drugs.

Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer.