The functions of mast cells in human graft-versus-host disease (GVHD) are unknown. We studied 56 patients who had an allogeneic hematopoietic cell transplantation (alloHCT) with a biopsy for diagnosis of gastrointestinal tract (GIT) GVHD before any treatment (including steroids): 35 with GIT GVHD, 21 HCT recipients whose biopsies did not confirm GVHD, and 9 with a new diagnosis of inflammatory bowel disease (IBD) as a comparison. The median number of mast cells (mean of CD117+ cells, counted in 3 selected spots under 40× magnification) was similar between patients with GVHD (59 cells) and those without GVHD (60 cells). However, the median number of mast cells was significantly associated with maximum clinical stage of GIT GVHD; the lowest counts of mast cells were observed in the highest clinical stage of GIT GVHD (stage 1, 80; stage 2, 69; stage 3, 54; stage 4, 26; P = .01). Moreover, every decrease by 10 mast cells was associated with increased nonrelapse mortality through 1 year (hazard ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .05). AlloHCT recipients all had significantly fewer mast cells, even those without GVHD compared with those with IBD (median, 59 vs 119; P < .01). The median number of GIT mast cells was also significantly lower in patients who received myeloablative conditioning (61.5 cells) than in those who received reduced intensity conditioning (78 cells) in the entire study population (P = .02). We conclude that GIT mast cells are depleted in all alloHCT patients, more prominently in those receiving myeloablative conditioning and those with severe GIT GVHD. Our novel findings warrant further investigation into the biological effects of mast cells in GIT GVHD.

Predictive prognostic scoring (PS) systems are not primarily applicable to elderly patients with classical Hodgkin lymphoma (cHL). The objective of this study was to develop a PS system for these patients. The derivation cohort (DC) was utilized for model development, consisting of 97 variables. The resulting algorithm was named as Hodgkin's Lymphoma Early Death in the Elderly within 12 months (HEDEL12). Internal and external validation cohorts (IVC and EVC) were employed for validation. A total of 286 patients were evaluated retrospectively. In DC 38 of 178 patients died within the first 12 months and overall survival (OS) at 12-month was 78.6%. Independent predictors of HEDEL12 were female sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4. According to HEDEL12 scores 0-1, OS at 12- months were 89.8% and 91.0% for IVC and EVC, respectively. The HEDEL12 scoring is useful in predicting the survival of advanced-stage cHL patients.

The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test strategies. The aim of this study is to introduce an artificial intelligence application as a more rational approach for testing JAK2 mutations in cases of erythrocytosis. Test results were sourced from samples sent to a tertiary hospital’s genetic laboratory between 2017 and 2023, meeting 2016 World Health Organization criteria for JAK2V617F mutation testing. The JAK2 Somatic Mutation Screening Kit was used for genetic testing. Machine learning models were trained and tested using Python programming language. Out of 458 cases, JAK2V617F mutation was identified in 13.3%. There were significant differences in complete blood count parameters between mutation carriers and non-carriers. Various models were trained with data, with the random forest (RF) model demonstrating superior precision, recall, F1-score, accuracy, and area under the receiver operating characteristic, all reaching 100%. Gradient boosting (GB) model also showed high scores. When compared with existing algorithms, the RF and GB models displayed superior performance. The RF and GB models outperformed other methods in accurately identifying and classifying erythrocytosis cases, offering potential reductions in unnecessary testing and costs.

In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy. Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results.

Karla Cavazos, Sheila Eswaran, Cathleen Maidlow, Fatma Keklik Karadag, Ramazan Idilman, Ilkay Idilman, Ira J Miller, Jamile Shammo, Nancy Reau, Celalettin Ustun

This study aimed to evaluate patients with RRMM who underwent daratumumab (DARA) therapy. This multicenter and retrospective study included 134 patients who underwent at least two courses of DARA from February 01, 2018 to April 15, 2022. Epidemiologic, disease and treatment characteristics of patients and, treatment related side effects were evaluated. Survival analysis were performed. The median age at initiation of DARA therapy was 60 (35-88) years. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The ORR after DARA therapy was 75 (55.9%), and ≥VGPR was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing DARA-Vd than for those undergoing DARA-Rd (16.9 vs. 8.3 months; p=0.014). Among patients undergoing Dara-Rd, PFS was higher in those without EMD (EMD-) than those with EMD (EMD+)(NA vs. 3.7 months; OR, 3.4; p < 0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provides OS and PFS advantage, although statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were grade 1-2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%; p < 0.001 and 42.9% vs. 15.7%; p < 0.001). Our study reflects real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.