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A 55-year-old man with acute myeloid leukemia began to have shortness of breath, cough with blood-tinged sputum, and hypoxemia 17 days after receiving a myeloablative allogeneic stem-cell transplant from a haploidentical donor.

The availability of data in longitudinal studies is often driven by features of the characteristics being studied. For example, clinical databases are increasingly being used for research to address longitudinal questions. Because visit times in such data are often driven by patient characteristics that may be related to the outcome being studied, the danger is that this will result in biased estimation compared to designed, prospective studies. We study longitudinal data that follow a generalized linear mixed model and use a log link to relate an informative visit process to random effects in the mixed model. This device allows us to elucidate which parameters are biased under the informative visit process and to what degree. We show that the informative visit process can badly bias estimators of parameters of covariates associated with the random effects, while allowing consistent estimation of other parameters.

Renal dysfunction in patients with acute myeloid leukemia (AML) can be multifactorial. We present the case of a 72‐year‐old male with relapsed myelomonocytic AML who presented with transient acute kidney injury (AKI) and severe persistent electrolyte derangements. In the setting of nephrotic‐range proteinuria and electrolyte wasting without significant albuminuria or glucosuria, a diagnosis of lysozymuria was made. Lysozymuria is a rare paraneoplastic complication of AML and chronic myelomonocytic leukemia characterized by lysozyme. This represents the first case of lysozymuria presenting primarily with refractory electrolyte derangements rather than severe AKI. Lysozymuria portends a poor clinical prognosis even with aggressive management.

Background Mouse double minute‐2 homolog (MDM2) plays a key role in downregulating p53 activity in hematologic malignancies, and its overexpression is associated with poor outcomes. Methods This phase 1 study assessed the safety and efficacy of different dosing regimens of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine (AZA) in patients with relapsed or refractory acute myeloid leukemia or high‐risk myelodysplastic syndromes. Results Seventy‐four patients (monotherapy, n = 57; milademetan‐AZA combination, n = 17) were treated. The maximum tolerated dose of milademetan was 160 mg once daily given for the first 14–21 days of 28‐day cycles as monotherapy and on Days 5–14 in combination with AZA. Dose‐limiting toxicities were gastrointestinal, fatigue, or renal/electrolyte abnormalities. Treatment‐emergent adverse events related to milademetan occurred in 82.5% and 64.7% of participants in the monotherapy and AZA combination arms, respectively. Two participants (4.2%) in the monotherapy arm achieved complete remission (CR), and 1 (2.1%) achieved CR with incomplete blood count recovery (CRi). Two participants (13.3%) achieved CRi in the combination arm. New TP53 mutations, detected only during milademetan monotherapy, were found pre‐existing below standard detection frequency by droplet digital polymerase chain reaction. Interpretation Milademetan was relatively well tolerated in this population; however, despite signals of activity, clinical efficacy was minimal.

Purpose of ReviewHematologic malignancies are common and difficult to treat in older adults. In this review, we focus on recent updates in diseases with several novel agents relevant to older adults—acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM).Recent FindingsIn AML, CPX-351 offers a new induction chemotherapy for secondary AML that prolongs survival, and venetoclax and IDH inhibitors are efficacious and well tolerated. In CLL, chemoimmunotherapy is being replaced by monoclonal antibodies and small molecule inhibitors that are more effective and better tolerated. In MM, new immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies have expanded treatment options for older patients.SummaryThe introduction of novel agents has dramatically shifted the landscape of therapeutic options for older adults with hematologic malignancies. Clinical trials in older adults are needed to expand treatment options for these patients.

Oral use of the selective FLT3 kinase inhibitor gilteritinib in patients who had relapsed or refractory acute myeloid leukemia with FLT3 mutations led to a median overall survival of 9.3 months (vs. 5.6 months with standard chemotherapy) and complete remission with full or partial hematologic recovery in 34.0% of patients (vs. 15.3%).

Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome 1 , 2 . AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Currently, AML treatment is initiated rapidly, precluding the ability to consider the mutational profile of a patient’s leukemia for treatment decisions. Untreated patients with AML ≥ 60 years were prospectively enrolled on the ongoing Beat AML trial (ClinicalTrials.gov NCT03013998 ), which aims to provide cytogenetic and mutational data within 7 days (d) from sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. A total of 487 patients with suspected AML were enrolled; 395 were eligible. Median age was 72 years (range 60–92 years; 38% ≥75 years); 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 d and were centrally assigned to a Beat AML sub-study; 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected standard of care (SOC) (103), investigational therapy (28) or palliative care (40); 9 died before treatment assignment. Demographic, laboratory and molecular characteristics were not significantly different between patients on the Beat AML sub-studies and those receiving SOC (induction with cytarabine + daunorubicin (7 + 3 or equivalent) or hypomethylation agent). Thirty-day mortality was less frequent and overall survival was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected SOC. A precision medicine therapy strategy in AML is feasible within 7 d, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival. Preliminary results from the Beat AML umbrella trial demonstrates the feasibility and efficacy of applying prospective genomic profiling for matching newly diagnosed patients with AML with targeted therapies.

Hematopoietic cell transplant (HCT) recipients are at risk for thromboembolic and bleeding complications. There is limited evidence regarding the optimal approach to managing venous thromboembolism (VTE) prophylaxis in hospitalized patients undergoing HCT. In this retrospective cohort study, we evaluated the incidence of bleeding and VTE events in hospitalized HCT patients who received VTE prophylaxis per our institution’s VTE Prophylaxis Protocol (VPP), with either enoxaparin 40 mg subcutaneously daily or heparin 5 000 units subcutaneously twice daily, compared to historical controls who did not receive VTE prophylaxis. The primary outcome was a composite of major bleeding events, clinically relevant non-major bleeding (CRNMB), and minor bleeding. The secondary outcome was a composite of VTE events. A total of 614 patients were evaluated, including 278 prior to and 336 after implementation of VPP. VTE prophylaxis resulted in no difference in bleeding events (15.1% in the pre-VPP group vs. 14.6% in the post-VPP group, p = 0.86) or composite of major and CRNMB events (0.72% vs. 0.30%, p = 0.59). There was a trend toward lower incidence of VTE events in the post-VPP group which did not reach statistical significance (8.6% vs. 6.0%, p = 0.20). We conclude that VTE prophylaxis does not pose additional bleeding risk in HCT patients.