Disseminated intravascular coagulation score evolution in 48 h predicts early death in acute promyelocytic leukemia patients.

INTRODUCTION: Early death (ED) is the unsolved issue of acute promyelocytic leukemia (APL). The disseminated intravascular coagulation (DIC) score has been proposed as a marker of bleeding and death in APL; whether its temporal evolution predicts outcomes in APL is unknown. We evaluated whether an increasing score 48 h after diagnosis associates with ED. METHODS: Retrospective, single-center study, including patients with newly diagnosed APL between 2000 and 2023, treated with all-transretinoic acid (ATRA) plus anthracycline or arsenic trioxide (ATO). "DIC score worsening" was defined as ≥1 point increase in the score after 48 h, and ED as death within 30 days of diagnosis. RESULTS: Eighty-six patients were included, with median age of 46 years (17-82). ED patients (26.7%) more frequently had age >60 years and worsening DIC score after 48 h. These were also the only predictors of ED identified in both univariate and multivariate (OR 4.18, p = .011; OR 7.8, p = .005, respectively) logistic regression analysis. CONCLUSION: This is the first study on DIC score evolution in APL-a worsening DIC score 48 h after diagnosis is a strong independent predictive factor of ED. We propose a reduction of the DIC score from diagnosis as a new treatment goal in APL care.

Predictors of very early death in acute promyelocytic leukemia: a retrospective real-world cohort study.

Early death (ED) is still the major obstacle to cure in acute promyelocytic leukemia (APL). Most studies focus on 30-day ED; however, little is known on predictors of death before starting APL treatment (very early death - VED) and on predictors of 7-day ED, the period with most deaths due to thrombohemorrhagic diathesis. We hypothesized whether the severity of the coagulopathy of APL could predict VED and 7-day ED. We also aimed to evaluate other characteristics associated with these outcomes. We undertook a retrospective, single-center observational study including newly diagnosed APL patients admitted to our institution between January 2000 and November 2022. Baseline demographical, clinical, and laboratorial data were collected. Statistical analysis was performed using Stata. One hundred four patients were included. The VED rate was 4.8%. A DIC Score ≥ 7 (p = 0.045), serum creatinine > 1.5 mg/dL (p < 0.001%), a DIC Score ≥ 6 within 24 h (p = 0.009), and mechanical ventilation (p < 0.001) were associated with VED. The 7-day ED rate was 12.5%. High-risk (p = 0.007) and hypogranular APL (p = 0.029), DIC Score at diagnosis (p = 0.047), DIC Score ≥ 7 (p = 0.043), DIC Score ≥ 6 within 24 h (p = 0.025), PT prolongation > 6 s (p = 0.002), and creatinine > 1.5 mg/dL (p = 0.004) were associated with 7-day ED. However, only elevated creatinine emerged as an independent predictor of 7-day ED (OR 21.4; p = 0.008). Our study shows that in patients with APL, an elevated creatinine at diagnosis strongly predicts for 7-day ED. A DIC Score ≥ 7 and a Score that remains ≥ 6 within 24 h and a serum creatinine > 1.5 mg/dL significantly associated with VED.

Cerebrovascular Complications of Anemia.

PURPOSE OF THE REVIEW: Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative review of the main cerebrovascular complications of anemia and its influence on stroke prognosis. RECENT FINDINGS: Both hypoproliferative anemia (thalassemia, iron deficiency anemia, etc.) and hyperproliferative anemia (sickle cell disease, paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis, etc.) are associated to cerebrovascular disease ranging from transient ischemic attack to ischemic stroke and hemorrhagic stroke with both intraparenchymal hemorrhage and subarachnoid hemorrhage or cerebral venous thrombosis. Anemia is associated to a worse prognosis in patients with cerebrovascular disease In some cases, like sickle cell disease, pathophysiological mechanisms and therapeutic guidelines are well established, while in others, due to their rarity, there are still lack of robust data. More studies are needed to clarify how the prognosis of stroke patients with anemia could be improved.

Correction to: Update on management and progress of novel therapeutics for R/R AML: an Iberian expert panel consensus.

After publication of this paper, the authors determined that an additional information in the funding section was missing.

Update on management and progress of novel therapeutics for R/R AML: an Iberian expert panel consensus.

A significant proportion of adult patients with acute myeloid leukemia (AML) fail to achieve complete remission or will relapse later on after achieving it. Prognosis for relapsed or refractory (R/R) AML patients remains discouraging, with the main curative option still relying on hematopoietic stem cell transplant (HSCT) for those who are eligible. Beyond morphological bone marrow and peripheral blood assessment, evaluation of patient performance status and comorbidities, as well as genetic/molecular characterization, is crucial to make an accurate diagnosis and prognosis, which will be useful to select the most appropriate treatment. Emerging strategies are mainly focusing on the development of immune- and molecular-based approaches. Novel targeted therapies are generally well tolerated, potentially allowing them to be administered alone or in combination with classical chemotherapy agents. Enrolment in clinical trials should be considered first option for R/R AML patients, either as a bridge to HSCT or to benefit from novel therapies that eventually may prolong survival and improve quality of life. An Iberian expert panel has reviewed the recent advances in the management of R/R AML with the aim to develop updated evidence and expert opinion-based recommendations.

Full-Dose Azacitidine in 5 Days Versus 7 Days With a Weekend Break in Myelodysplastic Syndromes: A Retrospective Cohort Study.

INTRODUCTION: Apart from transplantation, only azacitidine demonstrated a survival benefit in a phase III study in higher-risk myelodysplastic syndromes (MDS). The approved regimen is 75 mg/m2/day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules with 5 days and 7 days with a weekend break (5 + 2) have been used for convenience despite the lack of strong scientific support. Most studies of alternative schedules were performed in lower-risk MDS and with dose reduction in the 5-day schedules. METHODS: We performed a single-center, retrospective cohort study to compare full-dose azacitidine (7 × 75 mg/m2) administration in 5-day and 5 + 2-day schedules in a higher-risk MDS cohort. We evaluated 100 patients for overall survival and a subsample (49 patients) for acute myeloid leukemia-free survival (AMLFS), probability of infections and transfusion burden. Kaplan-Meier analysis and Cox models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate assessment. RESULTS: After a median follow-up of 10.8 months, patients treated with a 5-day schedule had a median overall survival of 12.5 months versus 15.0 months in the 5+2 group: HR 0.95 (95% CI, 0.57-1.56); P= .83. AMLFS was also similar between groups: HR 1.70 (95% CI, 0.70-4.14); P = .24. Azacitidine schedules were not predictive of infections nor number of red blood cell or platelet transfusions in multivariate analyses. CONCLUSIONS: In higher-risk MDS, full-dose azacitidine (7 × 75 mg/m2) can be administered both in 5 days and in 7 days with a weekend break with no significant difference in survival, infection or transfusional outcomes.

Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine.

VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.

Cerebrovascular manifestations in hematological diseases: an update.

Patients with hematological diseases often experience cerebrovascular complications including ischemic stroke, intracerebral and subarachnoid hemorrhage, microbleeds, posterior reversible encephalopathy syndrome, and dural sinus and cerebral vein thrombosis (CVT). In this update, we will review recent advances in the management of cerebrovascular diseases in the context of myeloproliferative neoplasms, leukemias, lymphomas, multiple myeloma, POEMS, paroxysmal nocturnal hemoglobinuria (PNH), thrombotic thrombocytopenic purpura (TTP), and sickle-cell disease. In acute ischemic stroke associated with hematological diseases, thrombectomy can in general be applied if there is a large vessel occlusion. Intravenous thrombolysis can be used in myeloproliferative neoplasms and sickle-cell anemia, but in other diseases, a case-by-case evaluation of the bleeding risks is mandatory. Patients with sickle-cell disease and acute stroke need very often to be transfused. In PNH, acute ischemic stroke patients must be anticoagulated. Most patients with CVT can be treated with low-molecular weight heparin (LMWH) acutely, even those with leukemias. Prevention of recurrence of cerebral thrombotic events depends on the control of the underlying disease, combined in some conditions with antithrombotic drugs. The recent introduction of specific monoclonal antibodies in the treatment of PHN and TTP has dramatically reduced the risk of arterial and venous thrombosis.

Spontaneous Tumor Lysis Syndrome: A Rare Presentation in Plasmablastic Lymphoma.

Tumor lysis syndrome is an oncological emergency, which can ultimately lead to death if not recognized early and treated accordingly. The institution of adequate prophylactic measures can decrease its incidence and severity; but very rarely, a highly aggressive neoplasm such as acute lymphoblastic leukemia or Burkitt's lymphoma can present with spontaneous tumor lysis syndrome (sTLS). We present the case of a 58-year-old male with newly diagnosed plasmablastic lymphoma with a retroperitoneal bulky mass invading the bladder, who presented with severe sTLS and was admitted to an intensive care unit due to acute renal failure and hyperkalemia requiring emergent renal replacement therapy. With urgent chemotherapy, several hemodialysis sessions and rasburicase, all the metabolic derangements were corrected and the patient fully recovered a normal renal function. This report highlights the importance of early recognition of sTLS in any patient presenting with severe and de novo multiple metabolic derangements involving uric acid, phosphorus, calcium and creatinine, even in patients with tumors not usually presenting with this complication.

Osteomyelitis Caused by Carbapenemase-Producing Klebsiella Pneumoniae: A Diagnosis to Consider in Patients with Hematologic Malignancies and Stem Cell Transplant Recipients.

BACKGROUND Osteomyelitis (OM) due to carbapenemase-producing Klebsiella pneumoniae (CPKp) is a very rare but severe condition, particularly among patients with hematologic malignancies and stem cell transplant recipients, who are especially at risk of developing nosocomial infections caused by this bacterium. CASE REPORT We describe 2 cases of acute and chronic OM by CPKp in adults with hematologic disorders. Patient 1, with acute lymphoblastic leukemia, developed bacteremia due to multidrug CPKp after induction chemotherapy. Despite pathogen-directed antibiotic treatment, blood cultures remained positive for CPKp, with an increase in its resistance pattern, and worsening of clinical condition. A pelvic computed tomography revealed air bubbles in the femoral head and ilium, suggestive of OM, and bone culture was positive for pandrug-resistant CPKp. The clinical condition deteriorated rapidly and the patient died. Patient 2, with aplastic anemia, developed multidrug CPKp bacteremia after immunosuppressive therapy, with good response to pathogen-directed antibiotic treatment. Ten months later, she underwent a hematopoietic stem cell transplant, and at the time of neutrophil engraftment, an abscess developed in the right thigh. An extensively drug-resistant CPKp was isolated from the pus, and antibiotics were started, without clinical improvement. A magnetic resonance of the thigh revealed an intraosseous abscess, suggestive of OM, and after debridement surgery and 6 weeks of parenteral antibiotics, she was successfully discharged home. CONCLUSIONS OM due to CPKp is uncommonly reported. These 2 cases illustrate the complex management of OM by CPKp in immunocompromised hematologic patients, and the importance of clinical suspicion for a prompt diagnosis, early treatment, and successful outcome.

Complete androgen insensitivity syndrome caused by a novel splice donor site mutation and activation of a cryptic splice donor site in the androgen receptor gene.

The androgen insensitivity syndrome is an X-linked recessive genetic disorder characterized by resistance to the actions of androgens in an individual with a male karyotype. We evaluated a 34-year-old female with primary amenorrhea and a 46,XY karyotype, with normal secondary sex characteristics, absence of uterus and ovaries, intra-abdominal testis, and elevated testosterone levels. Sequence analysis of the androgen receptor (AR) gene revealed a novel splice donor site mutation in intron 4 (c.2173+2T>C). RT-PCR analysis showed that this mutation resulted in the activation of a cryptic splice donor site located in the second half of exon 4 and in the synthesis of a shorter mRNA transcript and an in-frame deletion of 41 amino acids. This novel mutation associated with a rare mechanism of abnormal splicing further expands the spectrum of mutations associated with the androgen insensitivity syndrome and may contribute to the understanding of the molecular mechanisms involved in splicing defects.