Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.

Efficacy, Safety and Quality of Life of Pegcetacoplan in Japanese Patients With Paroxysmal Nocturnal Hemoglobinuria Treated Within the Phase 3 PEGASUS Trial.

INTRODUCTION: Pegcetacoplan, the first approved proximal complement C3 inhibitor, showed superiority to eculizumab in improving hemoglobin levels and clinical outcomes in the phase 3 PEGASUS study in patients with paroxysmal nocturnal hemoglobinuria (PNH) and inadequate response to eculizumab. METHODS: This analysis evaluates the efficacy and safety of pegcetacoplan for Japanese patients in PEGASUS, as they are known for different clinicopathologic features compared to non-Asian patients. Ten Japanese patients were enrolled to receive pegcetacoplan (n=5) or eculizumab (n=5) during the 16-week randomized controlled period. All patients received pegcetacoplan monotherapy during the open-label period until Week 48. RESULTS: Treatment with pegcetacoplan improved hemoglobin with a mean change from baseline of 2.4 g/dL at Week 16, which was sustained through 48 weeks. Pegcetacoplan-treated Japanese patients experienced sustained improvements in key secondary efficacy endpoints, including freedom from transfusion, lactate dehydrogenase level, reticulocyte count, and FACIT-Fatigue score. The safety profile was consistent with previously reported data from pegcetacoplan studies. No events of hemolysis, meningococcal infection, or thrombosis were reported in the Japanese population and all Japanese patients remained on treatment throughout the study. CONCLUSION: These data suggest that Japanese patients with PNH can be effectively and safely managed with pegcetacoplan. CLINICALTRIALS: gov identifier: NCT03500549.

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma.

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab-Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab-Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study.

BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/µL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.

Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study.

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel.

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B-cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B-cell lymphoma, follicular lymphoma with histologic transformation to large B-cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch.

BACKGROUND: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. STUDY DESIGN AND METHODS: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. RESULTS: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. CONCLUSION: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.

Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapy.

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T-cell therapy, an emerging therapy for relapsed or refractory diffuse large B-cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T-cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T-cell infusion in patients with PC. Cytokine analyses after CAR T-cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation-related cytokines on day 28 after CAR T-cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation-related cytokines in the BM following CAR T-cell infusion are associated with subsequent PC.

A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction.

A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

Association between early corticosteroid administration and long-term survival in non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation.

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs.

Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice.

Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10-10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.

Red blood cell depletion in small-volume bone marrow processing using manipulation with third-party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems.

BACKGROUND: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.

Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial.

BACKGROUND: In the PEGASUS trial, the complement C3 inhibitor, pegcetacoplan, showed superiority to eculizumab in improving haematological outcomes in adult patients with paroxysmal nocturnal haemoglobinuria and suboptimal response to eculizumab at 16 weeks. The aim of the open-label period was to evaluate the long-term efficacy and safety of pegcetacoplan through to 48 weeks. METHODS: PEGASUS was a phase 3, randomised, open-label, active-comparator controlled trial conducted in 44 centres in Australia, Belgium, Canada, France, Germany, Japan, Russia, South Korea, Spain, the UK, and the USA. Eligible participants were aged 18 years or older, had paroxysmal nocturnal haemoglobinuria, and had a haemoglobin concentration of less than 10·50 g/dL after 3 months or longer of stable eculizumab treatment. After a 4-week run-in with eculizumab plus pegcetacoplan, patients were randomly assigned (1:1) by interactive response technology to pegcetacoplan (1080 mg subcutaneously twice weekly) or eculizumab (according to their regimen at enrolment) for 16 weeks and could continue to the open-label period (32 weeks of pegcetacoplan monotherapy [pegcetacoplan-to-pegcetacoplan] or 28 weeks of pegcetacoplan monotherapy [eculizumab-to-pegcetacoplan]). Randomisation was stratified by platelet count and number of previous blood transfusions. The primary endpoint was change from baseline in haemoglobin at week 16, which has previously been reported. The outcomes of the open-label period (week 16 to week 48) are reported here. At 48 weeks, efficacy (including mean haemoglobin concentration and quality of life measured on the Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scale) was assessed in the intention-to-treat population and safety was assessed per protocol. This trial was registered with ClinicalTrials.gov, NCT03500549, and has been completed. FINDINGS: Between June 14, 2018, and Nov 14, 2019, 80 patients were randomly assigned to receive treatment with pegcetacoplan (41 patients) or eculizumab (39 patients). Most participants were women (49 [61%]) and 31 (39%) were men; 12 (15%) were Asian, two (3%) were Black, 49 (61%) were White, and 17 (21%) were another race or did not report their race. The open-label period had 77 participants (38 pegcetacoplan-to-pegcetacoplan, 39 eculizumab-to-pegcetacoplan). Patients in the pegcetacoplan-to-pegcetacoplan group maintained high mean haemoglobin concentrations between 16 weeks (11·54 g/dL [SD 1·96]) and 48 weeks (11·30 g/dL [1·77]; p=0·14). Patients in the eculizumab-to-pegcetacoplan group had significantly greater mean haemoglobin concentrations at 48 weeks (11·57 g/dL [2·21]) versus 16 weeks (8·58 g/dL [0·96]; p<0·0001). Clinically meaningful improvements in FACIT-Fatigue scores were observed at 48 weeks, with a mean change from baseline for all patients receiving pegcetacoplan monotherapy of 9·89 points (SD 9·63), for patients in the pegcetacoplan-to-pegcetacoplan group mean 10·14 points (9·06), and for patients in the eculizumab-to-pegcetacoplan group mean 9·62 points (10·34). During the entire study period, 13 (16%) of 80 patients discontinued treatment (three [7%] of 41 through to week 16 due to breakthrough haemolysis, and ten [13%] of 77 due to severe treatment-emergent adverse events) and 18 patients (eight pegcetacoplan-to-pegcetacoplan, ten eculizumab-to-pegcetacoplan) had at least one serious treatment-emergent adverse event during the open-label period, four were considered to be related to pegcetacoplan treatment. The most common treatment-emergent adverse events (in ≥10% patients) among both pegcetacoplan-treated groups during the open-label period were injection site reactions (in 20 [26%] of 77 patients), haemolysis (15 [19%]), nasopharyngitis (12 [16%]), and diarrhoea (ten [13%]). No treatment-related deaths occurred throughout the duration of the study. INTERPRETATION: The durability of improved haematological outcomes and favourable safety profile over 48 weeks of treatment suggests that pegcetacoplan has the potential to improve treatment benefit and alter treatment goals in patients with paroxysmal nocturnal haemoglobinuria. FUNDING: Apellis Pharmaceuticals.

Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients.

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection.

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/µl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.

Low hematocrit reduces the efficiency of CD34+ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure.

BACKGROUND: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. STUDY DESIGN AND METHODS: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. RESULTS: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p < .0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r = .47, p < .0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. CONCLUSION: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV.

Possible prognostic impact of WT1 mRNA expression at day + 30 after haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide for patients with myeloid neoplasm: a multicenter study from the Okayama Hematological Study Group.

BACKGROUND: Previous studies have revealed that relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be predicted by monitoring Wilms' tumor 1 (WT1) mRNA expression. However, only a few studies have investigated patients who received human leukocyte antigen-haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCY-haplo). In this study, we investigated the relationship between WT1 mRNA levels and clinical outcomes in the PTCY-haplo group, and compared them with those in the conventional graft-versus-host disease prophylaxis group (conventional group). METHODS: We retrospectively analyzed 130 patients who received their first allo-HSCT between April 2017 and December 2020, including 26 who received PTCY-haplo. RESULTS: The WT1 mRNA expression level at day + 30 after allo-HSCT associated with increased risk of 1-year cumulative incidence of relapse (CIR) was ≥ 78 copies/µg RNA in the conventional group (p < 0.01) and ≥ 50 copies/µg RNA in the PTCY-haplo group (p = 0.03). CONCLUSIONS: The appropriate cutoff level of WT1 mRNA at day + 30 after allo-HSCT for predicting prognosis in patients treated with PTCY-haplo may be < 50 copies/µg RNA.

Chronic active Epstein-Barr virus infection presenting as refractory chronic sinusitis.

A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein-Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis.