American Journal of Hematology最新文献

Acute chest syndrome (ACS) is one of the most common severe complications of sickle cell disease (SCD). In recent years, a major role of inflammation and innate immunity has been evidenced, but ACS pathophysiology remains incompletely understood, and therapeutic options are limited. We performed proteomic analysis of induced sputum and tracheal aspirates in eight SCD children during ACS (four intubated and four non-intubated) and in three during vaso-occlusive crisis (VOC) without ACS. Proteomic analysis revealed that one of the main canonical pathways involved during ACS was the complement system. To further investigate its implication, we measured the main components of the complement alternative and terminal pathways in sputum and plasma from SCD children during 27 ACS episodes compared with 16 VOC episodes without ACS. A dramatic increase in the median level of C3a, C5a, sC5b-9, factor B, factor D, properdin, and factor H was observed in the sputum from SCD children during ACS. In the plasma, no significant increase was observed during ACS compared to VOC, except for sC5b-9, whose median level was twofold higher than during VOC but 16-fold lower than the sC5b-9 median level in the sputum during ACS. Also, the C3a/C3 and C5a/C5 ratios were significantly increased in sputum compared to plasma during ACS, reflecting a predominant local pulmonary activation of the complement system compared to systemic activation. Our results reveal the potentially crucial role of complement activation in the lungs during ACS and open new therapeutic perspectives with anti-complement agents for this severe complication of SCD.

Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor-like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.

P. Kongtim, P. Chumnumsiriwath, P. Vittayawacharin, D. Jeyakumar, B. J. Lee, J. Doh, S. P. Griffin, R. A. Van Etten, and S. Ciurea, “Budesonide, Added to PTCy-Based Regimen, for Prevention of Acute GI GVHD After Allogeneic Stem Cell Transplantation,” American Journal of Hematology 100 (2025): 383–392, https://doi.org/10.1002/ajh.27581.

In the funding section on the first page of the article stated “Funding: The authors received no specific funding for this work.” Was incorrect.

This should have read: Funding: This dataset was collected by the Center for International Blood and Marrow Transplant Research (CIBMTR), which is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases; 75R60222C00011 from the Health Resources and Services Administration; N00014-25-1-2146 from the Office of Naval Research; NMDP; and the Medical College of Wisconsin.

We apologize for this error.

A 64-year-old woman presented to the hematology clinic for follow up of refractory chronic cold agglutinin disease with hepatic iron overload secondary to a chronic red cell transfusion burden. Management had included single-agent rituximab and ciclosporin, to which the disease had proven refractory. She had recently received a first cycle of bendamustine and rituximab. On review preceding a second cycle, she was tired and lightheaded and scleral icterus was noted. A blood sample was taken urgently and conveyed to the laboratory for testing. Full blood count results, compared to results from three weeks earlier, are tabulated.

Given the unexpected abnormalities in the blood count, an urgent blood film was made. This showed only small red cell agglutinates (left image, ×100 objective) and did not confirm the apparent thrombocytosis. The most striking feature was the presence of numerous red cell fragments, many of which were spherical and some of which were budding from red cells (both images). There were small numbers of more angular fragments. The thrombocytosis was factitious and attributable to schistocytes being counted as platelets. The leucocytosis was also factitious and attributable to loose clumps of platelets and debris being counted as leucocytes. All neutrophils were cytologically abnormal with blurred nuclear and cytoplasmic outlines and increased granularity (right image). The findings were not suggestive of a microangiopathic hemolytic anemia since the schistocytes were not often angular but rather were often microspherocytes and could be seen budding from red cells. These findings suggest the effect of heat. These distinctive heat effects can be seen both in patients suffering from burns and also when a blood sample has been inappropriately heated in vitro. Further investigation revealed that the phlebotomist had transported the patient's blood specimen to the laboratory in a mug of hot water.

Erroneous results of a blood count can result from preanalytical, analytical, or post-analytical errors. This is an example of an uncommon preanalytical error. It is important that when it is necessary to keep a blood specimen warm it is kept at a controlled temperature of 37°C. Staff training is also important.

The authors declare no conflicts of interest.

There is limited information regarding the contemporary real-world clinical and financial burden of Medicaid enrollees with sickle cell disease (SCD) in the United States. Using the IBM MarketScan Medicaid database (7/2016–12/2020), individuals with ≥ 3 SCD diagnoses were matched 1:1 on age, gender, and race to individuals without SCD. Continuous coverage was required during 6-month baseline and 12-month follow-up periods. Follow-up healthcare resource utilization (HCRU) and costs were compared between the SCD and non-SCD cohorts in separate analyses of the pediatric (< 18 years, n = 4723 per cohort, 52% male, mean age: 8.8 years) and adult (≥ 18 years, n = 5597 per cohort, 60% female, mean age: 35.1 years) populations. During follow-up, pediatric individuals with SCD had significantly more hospitalizations (0.8 vs. 0.03) with longer length of stay (LOS, 3.0 vs. 0.1 days), outpatient visits (19.5 vs. 10.8), prescriptions (12.8 vs. 3.8), and higher mean total costs ($18 900 vs. $2127) than individuals without SCD; hospitalizations (39.6-fold) and pharmacy use (11.9-fold) accounted for the largest cost differences. Adults with SCD had significantly more hospitalizations (2.1 vs. 0.1; LOS: 11.3 vs. 0.7 days), outpatient visits (46.5 vs. 22.5), office visits (7.7 vs. 4.9), prescriptions (29.5 vs. 13.7), and higher mean total costs ($45 114 vs. $6039) than adults without SCD; hospitalizations (18.7-fold) and ER visits (12.7-fold) had the greatest cost differences. In conclusion, pediatric and adult Medicaid enrollees with SCD had significantly higher HCRU and costs, demonstrating an unmet need for improved management of SCD to potentially reduce the economic burden for both payers and individuals with SCD.

Sickle cell anemia (SCA) leads to reduced physical functioning and cardiopulmonary fitness. Prior studies suggest that airway hyperresponsiveness to bronchoprovocation testing is common in SCA, but the prevalence of exercise-induced bronchospasm (EIB) is understudied. We hypothesized that EIB is more common in children with SCA than in controls. Non-asthmatic subjects 10–21 years old with SCA and race-matched controls underwent (1) maximal Cardiopulmonary Exercise Testing (CPET) by cycle ergometry and (2) a Controlled Intensity Interval Test (CIIT) consisting of eight bouts of constant workload cycling, randomized to 50% (moderate) or 70% (vigorous) of peak workload. Spirometry was performed pre/post CPET and CIIT. Multivariable logistic regression models tested associations between SCA status and EIB in response to CPET and CIIT. Compared to controls, subjects with SCA demonstrated lower hemoglobin, reduced baseline spirometry values, and decreased CPET maximal workload. Baseline lower airway obstruction and completion rates for CPET and CIIT were similar between groups. No adverse events occurred. The percentage of participants who met criteria for EIB did not differ between subjects and controls after CPET (21% vs. 26%, p = 0.537) or CIIT (32% vs. 17%, p = 0.126). In adjusted models, SCA status was not associated with EIB after CPET or CIIT. EIB was not more common in subjects with SCA versus controls after maximal CPET or submaximal exercise challenge of longer duration. Further research is needed to inform the development of exercise guidelines and to better understand the effects of exercise on airway dynamics in SCA.

Trial Registration: ClinicalTrials.gov identifier: NCT03653676.