Abstract Background The optimal conditioning regimen for alloHCT in children with myeloid malignancies remains undefined. Procedure We performed a retrospective review of children undergoing alloHCT for AML and MDS over a 10‐year period (2008‐2018) at our institution, comparing the outcomes of recipients of either a myeloablative busulfan‐ or reduced toxicity mel/thio‐based conditioning regimen. Results A total of 49 patients underwent alloHCT for AML/MDS (mel/thio, N = 21; busulfan, N = 28). Mel/thio recipients were selected due to pretransplant comorbidities. Recipients of mel/thio were more likely to have t‐AML, and less likely to have MRD <0.1% at the time of alloHCT (57.1% vs 82.1%). Graft failure was more common in busulfan recipients; engraftment kinetics were similar between groups. Sinusoidal obstructive syndrome was diagnosed in 21% of busulfan and no mel/thio recipients ( P = .03). One patient in each group died from TRM. Relapse incidence was comparable (mel/thio—29% vs busulfan—32%); however, relapse occurred significantly later in recipients of mel/thio conditioning (median d + 396 vs d + 137; P = .01). As a result, there was a trend toward improved OS at 1 and 3 years in mel/thio recipients (95% vs 74%, P = .06; and 75% vs 50%, P = .11; respectively). Conclusion In our single institution, when compared to myeloablative busulfan‐based conditioning, use of a mel/thio‐based reduced toxicity regimen resulted in comparable outcomes, despite higher risk patient and disease characteristics. Mel/thio recipients had both more comorbidities and higher risk disease profile, which did not translate into higher rates of either TRM or relapse.
Platelet inhibition after aspirin therapy reduces the risk for the development of acute coronary syndromes. However, the mechanism by which aspirin affect platelets other than by prostaglandin blockade is unclear. We sought to determine thein vitroeffects of aspirin on the surface expression of nine platelet receptors using whole blood flow cytometry. Blood from 24 healthy volunteers was incubated for 30 min with 1.8 and 7.2 mg/l phosphatebuffered saline-diluted acetylsalicylic acid in the presence or absence of apyrase. Platelet serotonin release, and the surface expression of platelet receptors with or without apyrase were determined using the following monoclonal antibodies: anit-CD41 [glycoprotein (GP)IIb/IIIa], CD42b (GPIb), CD62p (P-selectin), CD51/CD61 (vitronectin receptor), CD31 [platelet/endothelial cellular adhesion molecule-1 (PECAM-1)], CD107a [lysosomal associated membrane protein (LAMP)-1], CD107b (LAMP-2), CD63 (LIMP or LAMP-3), and CD151 (PETA-3). Samples were then immediately fixed with 2% paraformaldehyde, and run on the flow cytometer within 48 h. Aspirin does not affect serotonin release from human platelets. Dose-dependent inhibition of GPIIb/IIIa, P-selectin, CD63, and CD107a receptor expression was observed in the aspirin-treated whole-blood samples. Apyrase potentiates the effects of aspirin, and independently inhibits PECAM-1. In addition to the known effect of irreversibly inhibiting platelet cyclooxygenase-1, thereby blocking thromboxane A2 synthesis, it appears that aspirin exhibits direct effects on selective major platelet receptors.Blood Coagul Fibrinolysis14:249-253 & 2003 Lippincott Williams & Wilkins.
Liver dysfunction is common after pediatric hematopoietic stem cell transplantation (HSCT) and liver biopsy may be necessary to diagnosis the cause of liver dysfunction and institute therapy. We report our liver biopsy experience in 356 consecutive patients. During the study period, 16 (4.5%) patients underwent 18 biopsies, all after allogeneic HSCT. The median time from HSCT to biopsy was 205.5 days. All patients had transaminase elevation and 67% had hyperbilirubinemia. The most commonly used method of biopsy was the imaging-guided percutaneous approach, performed in 12 of 18 cases. Five biopsies were done transjugularly and 1 was performed during laparotomy. In all the cases a histopathologic diagnosis was made. The most common diagnosis was graft-versus-host disease (GVHD) followed by iron overload. In 12 cases, management was modified based on biopsy results. Complications occurred after 5 biopsies, 4 of which were performed transjugularly. The most common complication was hemorrhage. Two patients required transfer to the intensive care unit for related complications. No complications were observed after percutaneous biopsies. In 2 cases a second procedure was required to manage the complication. We conclude that while liver biopsy yields a high-rate of diagnoses, it is accompanied by high rates of complications, particularly when the transjugular approach is used.
Background: Our group and others (Greinix BBMT 2015) have shown that higher proportions of recent thymic emigrants (RTEs: CD4+CD45RA+CD31+) at d100 are a prognostic biomarker for chronic GvHD in adults. We sought to understand whether RTEs, as well as regulatory T cells (CD4+CD25+CD127Lo) that co-express naïve and recently emigrated markers (CD45RA+CD31+; Treg RTEs) were prognostic at d100 for pediatric cGvHD. Methods: Allo-HCT patients (<18yrs) with malignant and non-malignant diagnoses were enrolled before HCT and prospectively followed for cGvHD until 1-year post-HCT. Blood was analyzed by 8-color flow cytometry at d100 (+/- 14d) for prognostic cellular cGvHD biomarkers. Mean values are reported. Biomarkers were considered clinically significant if means were >1.5× or <0.7× the control and P < .05. Two hundred and twelve patients were enrolled before June 30, 2016: 144 were evaluable with 1-year follow up and 68 excluded for relapse, non-engraftment or early death. Of the evaluable patients, 37 (25.7%) developed NIH criteria cGvHD, 34 (23.6%) had late aGvHD but no cGvHD, and 73 (50.7%) had no cGvHD. The no cGvHD group included patients both with and without a past history aGvHD, as we found previous aGvHD had no impact on d100 RTE and Treg RTE percentages in the absence of cGvHD. Late aGvHD was evaluated as a separate group independent of the cGvHD group. Results: RTEs as a % of CD4 T cells were significantly lower at d100 in patients with cGvHD compared to no cGvHD, and were prognostic for the later development of cGvHD (Table 1). Similar relationships existed for Treg RTEs, being significantly lower in cGvHD compared to no cGvHD. To determine whether RTEs and Treg RTEs were prognostic for any form of GvHD after d100, a combined group of cGvHD and late aGvHD was created and compared to the no cGvHD group. Both RTEs and Treg RTEs were significantly lower at d100 compared to the no cGvHD group and were prognostic for the development of any form of GvHD after d100.Table 1Cell PopulationNo cGvHDcGvHD onlyP-value*(AUC)Late aGvHD onlyP-value*(AUC)cGvHD + Late aGVHDP-value*(AUC)RTEs (% of CD4 T cells)13.5%7.8%.007 (.64)9.4%.08 (NS)8.5%.009 (.62)Treg RTEs (% of Tregs)13.2%6.4%.002 (.67)9.1%.06 (NS)7.6%.004 (.62)AUC, Area under curve on receiver operator curve.*Compared to the no cGvHD group. Open table in a new tab AUC, Area under curve on receiver operator curve. *Compared to the no cGvHD group. Conclusions: In this multi-institution study, both RTEs and Treg RTEs at d100 were prognostic biomarkers for pediatric cGvHD, irrespective of a previous history of aGvHD before d100. Interestingly, both T cell populations were lower compared to the no cGvHD group, a finding that is opposite to what our group and others have observed in adults with cGvHD. In a combined analysis of both late aGvHD and cGvHD, lower RTEs and Treg RTEs were also prognostic for GvHD after d100. These data suggest that thymic function may play a larger role in the later development of GvHD post-HCT for children compared to adults.
