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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14-74) vs. 67 (45-72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49-81%] and 58% (95% CI = 38-75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48-89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28-83%) vs. reduced-intensity conditioning = 55% (95% CI = 28-76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8-50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN.

Summary:Twenty-one paediatric patients (11 males and 10 females) received a CD34-selected partially matched related donor transplant for malignant (16 cases) and non-malignant conditions (five cases). The average cell dose was 11.13 ؋ 10 6 /kg. Fifteen of 16 patients with malignant conditions and one with non-malignant disease received total body irradiation plus cyclophosphamide. Three of 5 patients with non-malignant conditions and one with leukaemia, received busulphan plus cyclophosphamide. One patient with Fanconi anaemia received 100 mg/kg of cyclophosphamide. Fludarabine (25 mg/m 2 /day for 5 days) was administered prior to all these regimens. Additionally, anti-lymphocyte gamma-globulin (12.5 mg/kg/day) was administered from day ؊2 to day +2. Three (15%) patients failed to achieve complete chimaerism (CC). These patients received a second cell infusion. Two of them achieved CC. In the third patient, the percentage of donor cells was increased. The likelihood for engraftment was not related to the cell dose received. Acute graft-versus-host disease (GVHD) occurred in nine patients but only one developed GVHD Ͼgrade II. Eight patients developed active viral infections, which resolved after treatment. Patients receiving cell doses higher than our average had a significantly faster CD3 and CD4 cell recovery and experienced a lower incidence of viral infections. After 480 ؎ 255 days of median follow-up, 16/21 patients are alive and well and have CC. Three patients died of leukaemic relapse and a fourth from progression of his disease (adreno-leuko-dystrophy). We conclude that partially matched related donors are a feasible source of haemopoietic progenitor cells for transplantation for patients without matched familial or unrelated donors.

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are major limitations of chimeric antigen receptor (CAR) T-cell therapy. 1 Although tocilizumab, an anti-interleukin-6R (IL-6R) antibody, can ameliorate CRS, it has limited effectiveness in ICANS. 1,2 Systemic high-dose corticosteroids and supportive care are the current mainstay therapies for ICANS. Because infiltration of immune effector cells (IECs) into the central nervous system (CNS) 3 is implicated in ICANS, we administered intrathecal (IT) chemotherapy for steroid-refractory ICANS with rapid resolution of toxicities. We describe the clinical course and outcomes of 2 patients with steroidrefractory ICANS treated with IT chemotherapy. Institutional Review Board submission was deferred per institutional policy for case series that include ,3 patients. A 71-year-old man with chemorefractory diffuse large B-cell lymphoma (DLBCL) received secondgeneration 41BB CD3z anti-CD19 anti-CD20 (LV20.19) bispecific CAR T cells on a phase 1 clinical trial (NCT03019055). On day 15 post-LV20.19 CAR infusion, the patient developed grade 2 CRS that resolved with tocilizumab. On day 17, he developed grade 2 neurotoxicity by Common Terminology Criteria for Adverse Events v5. Treatment with dexamethasone, 10 mg every 6 hours, was initiated. With rapid improvement, his dexamethasone was tapered. Unfortunately, he progressed with grade 3 neurotoxicity on day 113 that was manifested by tremor, mutism, and nonresponsiveness. Lumbar puncture (LP) was performed, and cerebrospinal fluid (CSF) analysis revealed a white blood cell (WBC) count of 18 cells per microliter (Figure 1A), with a predominantly non-CAR CD4 1 T-cell population (Figure 1B). Pulse IV SOLU-MEDROL, 500 mg 3 3 days, was initiated, followed by dexamethasone, 10 mg every 6 hours, without any clinical improvement. Brain magnetic resonance imaging did not reveal any significant intracranial abnormality. An electroencephalogram was negative for seizures, and the patient was diagnosed with steroid-refractory ICANS.

Alternative donor allogeneic hematopoietic cell transplants (HCTs), such as double umbilical cord blood transplants (dUCBT) and haploidentical related donor transplants (haplo-HCT), have been shown to be safe and effective in adult patients who do not have an HLA-identical sibling or unrelated donor available. Most transplant centers have committed to 1 of the 2 alternative donor sources, even with a lack of published randomized data directly comparing outcomes and comparative data on the cost-effectiveness of dUCBT versus haplo-HCT. We conducted a retrospective study to evaluate and compare the early costs and charges of haplo-HCT and dUCBT in the first 100 days at 2 US transplant centers. Forty-nine recipients of haplo-HCT (at 1 center) and 37 with dUCBT (at another center) were included in the analysis. We compared graft acquisition, inpatient/outpatient, and total charges in the first 100 days. The results of the analysis showed a significantly lower cost of graft acquisition and lower total charges (for 100-day HCT survivors) in favor of haplo-HCT. Importantly, to control for the obvious shortcomings of comparing costs at 2 different transplant centers, adjustments were made based on the current (2018) local wage index and inflation rate. In the absence of further guidance from a prospective study, the cost analysis in this study suggests that haplo-HCT may result in early cost savings over dUCBT and may be preferred by transplant centers and for patients with more limited resources.

T cell-replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34 stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade < 2) was not associated with differences in overall survival or nonrelapse mortality. Severe CRS was associated with a statistically nonsignificant trend toward higher incidences of grades III to IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T cell-replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.

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