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BackgroundPediatric-inspired non-transplant regimens for adolescent and adult ALL patients are becoming standard in many institutions. We aimed to compare a cohort of patients receiving a pediatric-inspired protocol to a cohort of patients treated with adult type ALL therapy followed by allografting after achieving CR1.MethodEighty-five adolescent and adult ALL patients treated with CALGB 19802 protocol who received MSD transplant in CR1 were retrospectively compared to a matched cohort of 72 adolescent and adult ALL patients treated with a modified version of Children’s Cancer Group (CCG) 1900 protocol.ResultsThe five years OS in the allo-HCT cohort was 63.1% compared to 80.2% in the pediatric-inspired chemotherapy arm (P = 0.03). The five years EFS in the allo-HCT arm was 58.8% compared to 61.6% in the pediatric-inspired chemotherapy arm (P = 0.07). The five years DFS in the allo-HCT arm was 58.8% as compared to 71.9% in the pediatric-inspired chemotherapy arm (P = 0.07). The relapse rate in the allo-HCT cohort was 30.58% compared to 21.68% in the pediatric-inspired chemotherapy arm (P = 0.16). The NRM in the allo-HCT cohort was 10.59 as compared to 6.45 in the pediatric-inspired chemotherapy arm (P = 0.3).ConclusionFor adolescent and adult patients with Ph-negative ALL, pediatric-inspired chemotherapy resulted in higher OS compared to allo-HCT.

Chimeric antigen receptor (CAR) T‐cell therapy is a highly effective treatment for relapsed or refractory large B‐cell lymphoma (LBCL), but clinical experience in people living with HIV (PLWH) remains limited due to their exclusion from pivotal trials. We report the case of a 55‐year‐old man with HIV and high‐grade B‐cell lymphoma who developed severe anaphylaxis during axicabtagene ciloleucel (axi‐cel) infusion, requiring early termination after approximately 50% of the planned dose was delivered. The patient experienced only Grade 1 cytokine release syndrome and no neurotoxicity. Despite incomplete infusion, he achieved a sustained partial metabolic response on PET/CT imaging at Days +30, +60, and +110 post‐infusion. HIV remained well‐controlled throughout, and no infectious complications were observed. This case highlights both the feasibility of administering CAR T‐cell therapy in virologically suppressed PLWH and the potential for clinical benefit even with partial cell delivery. In addition, it draws attention to anaphylaxis as a rare but serious infusion‐related adverse event. To our knowledge, this is the first report of anaphylaxis to axi‐cel in a PLWH. The case underscores the need for enhanced pharmacovigilance and pre‐infusion risk assessment. It also supports growing evidence that PLWH should not be categorically excluded from CAR T‐cell access or clinical trials.

BackgroundAcute myeloid leukemia (AML) is a hematological malignancy that remains a therapeutic challenge due to the high incidence of disease relapse. To better understand resistance mechanisms and identify novel therapies, robust preclinical models mimicking the bone marrow (BM) microenvironment are needed. This study aimed to achieve an automated fabrication process of a three-dimensional (3D) AML disease model that recapitulates the 3D spatial structure of the BM microenvironment and applies to drug screening and investigational studies.MethodsTo build this model, we investigated a unique class of tetramer peptides with an innate ability to self-assemble into stable hydrogel. An automated robotic bioprinting process was established to fabricate a 3D BM (niche-like) multicellular AML disease model comprised of leukemia cells and the BM’s stromal and endothelial cellular fractions. In addition, monoculture and dual-culture models were also fabricated. Leukemia cell compatibility, functionalities (in vitro and in vivo), and drug assessment studies using our model were performed. In addition, RNAseq and gene expression analysis using TaqMan arrays were also performed on 3D cultured stromal cells and primary leukemia cells.ResultsThe selected peptide hydrogel formed a highly porous network of nanofibers with mechanical properties similar to the BM extracellular matrix. The robotic bioprinter and the novel quadruple coaxial nozzle enabled the automated fabrication of a 3D BM niche-like AML disease model with controlled deposition of multiple cell types into the model. This model supported the viability and growth of primary leukemic, endothelial, and stromal cells and recapitulated cell-cell and cell-ECM interactions. In addition, AML cells in our model possessed quiescent characteristics with improved chemoresistance attributes, resembling more the native conditions as indicated by our in vivo results. Moreover, the whole transcriptome data demonstrated the effect of 3D culture on enhancing BM niche cell characteristics. We identified molecular pathways upregulated in AML cells in our 3D model that might contribute to AML drug resistance and disease relapse.ConclusionsOur results demonstrate the importance of developing 3D biomimicry models that closely recapitulate the in vivo conditions to gain deeper insights into drug resistance mechanisms and novel therapy development. These models can also improve personalized medicine by testing patient-specific treatments.

Abstract Priming donors with G-CSF before BM harvest is reported to improve engraftment and GvHD in recipients. These effects are highly desirable when transplanting patients with non-neoplastic hematologic diseases, particularly AA patients. Here we retrospectively report the outcomes of 39 AA patients receiving a primed BM graft from MSD to 43 patients receiving a steady-state BM graft from MSD, otherwise transplanted using a uniform transplant platform. The graft had higher TNC and CD34 cell concentrations in the primed group (p < 0.001), and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group (p = 0.004 and 0.03, respectively). The OS for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients, p-value = 0.01. The cumulative incidence of death without GF was 2.6% in the primed group and 16.3% in the steady-state group, p-value = 0.03. There was no difference in GvHD incidence between the two groups. We confirm that priming improved the TNC and CD34 graft concentration and cell dose; this evidence along with other reported studies constitute reasonable evidence to prove that BM priming improve engraftment. We observed no increase in GvHD using primed BM graft.

Central nervous system (CNS) involvement by mantle cell lymphoma (MCL) is rare and portends a poor prognosis. We describe the first patient to have a complete response with front‐line treatment with single‐agent acalabrutinib for MCL CNS.

Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy‐related AML. Large registry‐based data identified sAML as an independent poor‐outcome type of AML post allogeneic hematopoietic cell transplantation (allo‐HCT). In our study, we tried to define factors affecting outcomes of sAML post allo‐HCT, and identify patients with sAML who may truly benefit from allo‐HCT. We retrospectively analyzed the data of 64 patients aged (14‐61 years) with sAML who received allo‐HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor‐risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease‐free survival (DFS; P‐value = .009, and .004, respectively). The cumulative incidence of chronic graft‐versus‐host disease (cGVHD) was significantly lower in sAML patients with poor‐risk cytogenetics (P‐value = .003) resulting in a high risk of death without cGVHD in this group of patients (P‐value = .02). Besides, GVHD relapse‐free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II‐IV cGVHD in the first 2 years post allo‐HCT. We conclude that sAML patients with poor‐risk cytogenetics have a significantly lower DFS post allo‐HCT with a high risk of death without active cGVHD.

Background/Aims: Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B (CHB) infection. This study evaluated the efficacy of TDF in achieving undetectable HBV DNA after 48 weeks of treatment in a Saudi cohort of CHB patients. Patients and Methods: This retrospective study included patients treated at a tertiary care center in Saudi Arabia from January 2009 to December 2012. Of the 68 eligible patients, 51 were treatment naïve and 17 were treatment-refractory. Twenty-three patients tested positive for HBeAg. The remaining 45 patients were HBeAg-negative. Results: The mean HBV DNA viral load decreased from 95 million IU/mL at baseline to 263 IU/mL after 48 weeks of treatment (P < 0.001). Overall, 62% of patients achieved a complete virological response (CVR) and 37% a partial virological response (PVR). Respective CVR and PVR rates according to subgroup were: HBeAg-positive (21.7% and 78.3%) and HBeAg-negative (84.4% and 15.6%). At 48 weeks, HBV DNA was undetectable in 66.7% of treatment-naïve and 53% of treatment-refractory patients (P = 0.3). Seroconversion occurred in 13 (57%) of HBeAg-positive patients. Two (3%) of the HBeAg-negative patients lost HBsAg at follow up. Mean alanine aminotransferase decreased significantly from 134 U/L before treatment to 37 U/L at 48 weeks (P < 0.001). Significant adverse events were not encountered during the study period. Conclusion: Forty-eight weeks of treatment with TDF reduced HBV DNA to undetectable levels in more than half of our patients regardless of whether they were treatment-naïve or refractory. HBeAg-negative (vs positive) patients experienced a better response rate.

PGF is a devastating complication after allogeneic transplant. We retrospectively analyzed our haploidentical transplant registry to report the incidence and impact of DSA and anti-HLA on engraftment. 107 patients were identified. Median recipient-age of 22, median donor-age of 31. Sixty-two patients had AML (58%), 29 had ALL (27%), 16 (15%) had other malignancies. Sixty-one recipients (57%) had positive anti-HLA, 56 of them had the DSA results available, of these 17 patients had DSAs (15% of the total number of patients, or 28% of patients who have anti-HLA antibodies). The median cumulative MFI was 2062. Sixty-three percent of the DSA were against class-II HLA antigens. The OS, CIR, aGvHD, and cGvHD did not differ between patients with and without anti-HLA antibodies, nor between patients with and without DSA. The gender of the recipient and donor, as well as the gender mismatch between recipient and donor, were statistically associated with the incidence of anti-HLA antibodies. Three patients only developed GF (2.8%), one was primary (0.9%) and the other two secondary GF (1.9%). None of the GF cases was in patients with anti-HLA antibodies or DSA. The presence of anti-HLA or DSAs did not affect the outcomes including the incidence of PGF.

Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B (CHB) infection. This study evaluated the efficacy of TDF in achieving undetectable HBV DNA after 48 weeks of treatment in a Saudi cohort of CHB patients. This retrospective study included patients treated at a tertiary care center in Saudi Arabia from January 2009 to December 2012. Of the 68 eligible patients, 51 were treatment naïve and 17 were treatment-refractory. Twenty-three patients tested positive for HBeAg. The remaining 45 patients were HBeAg-negative. The mean HBV DNA viral load decreased from 95 million IU/mL at baseline to 263 IU/mL after 48 weeks of treatment (P < 0.001). Overall, 62 of patients achieved a complete virological response (CVR) and 37 a partial virological response (PVR). Respective CVR and PVR rates according to subgroup were: HBeAg-positive (21.7 and 78.3) and HBeAg-negative (84.4 and 15.6). At 48 weeks, HBV DNA was undetectable in 66.7 of treatment-naïve and 53 of treatment-refractory patients (P = 0.3). Seroconversion occurred in 13 (57) of HBeAg-positive patients. Two (3) of the HBeAg-negative patients lost HBsAg at follow up. Mean alanine aminotransferase decreased significantly from 134 U/L before treatment to 37 U/L at 48 weeks (P < 0.001). Significant adverse events were not encountered during the study period. Forty-eight weeks of treatment with TDF reduced HBV DNA to undetectable levels in more than half of our patients regardless of whether they were treatment-naïve or refractory. HBeAg-negative (vs positive) patients experienced a better response rate.