InsT-ALLing CD7 chimeric antigen receptors before transplantation.

In their paper, the authors present their experience with the use of chimeric antigen receptor T cells targeting CD7 as a bridge to allogeneic haematopoietic cell transplantation in patients with relapsed/refractory T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma. Commentary on: Cao et al. A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy. Br J Haematol 2024;204:2351-2364.

RhD mismatch does not affect haematopoietic recovery, graft-versus-host disease and survival in allogeneic haematopoietic cell transplantation: A Japanese registry-based study.

BACKGROUND AND OBJECTIVES: ABO blood group mismatch between the donor and the recipient can affect the success of the transplant as well as problems with the red blood cells during allogeneic haematopoietic cell transplantation (HCT). However, the impact of the Rhesus (Rh) D mismatch on transplant outcomes in allogeneic HCT has been poorly elucidated. MATERIALS AND METHODS: We retrospectively evaluated the impact of the RhD mismatch on post-transplant outcomes in 64,923 patients who underwent allogeneic HCT between 2000 and 2021 using a Japanese registry database. RESULTS: Out of the whole group, 64,293, 322, 270 and 38 HCTs were done when the recipient or donor was RhD-mismatched with (+/+), (-/+), (+/-) or (-/-) combinations. The difference in RhD between recipient/donor (-/+), (+/-) and (-/-) did not affect haematopoietic recovery, acute and chronic graft-versus-host disease (GVHD), overall survival (OS), non-relapse mortality (NRM) or relapse when RhD (+/+) was used as the reference group in multivariate analysis. CONCLUSION: Our registry-based study demonstrated that RhD mismatch between recipient and donor did not significantly impact haematopoietic recovery, GVHD, OS, NRM or relapse after allogeneic HCT. These data suggest that RhD mismatches may not need to be avoided for recipient and donor combinations in allogeneic HCT.

The Simplified Comorbidity Index predicts non-relapse mortality in reduced-intensity conditioning allogeneic haematopoietic cell transplantation.

Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.

A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors-A single-centre, prospective, explorative study.

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.

Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission.

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD-], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16-24) months were studied. The incidence of grades II-IV and grades III-IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD- cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39-4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23-3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04-3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10-2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Age-related immune cell dynamics influence outcomes after allogeneic haematopoietic cell transplantation.

An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post-transplant immune recovery have been largely investigated across multiple cohorts issuing heterogeneous results. Differences in outcomes in adult and paediatric populations suggest an age-related contribution to post-transplant immune reconstitution; however, it is unclear how recipient and donor age may affect the dynamics of single immune cells. Here, we retrospectively collected and analysed immunological data of 174 patients (58 children and 116 adults) consecutively transplanted for haematological disorders in our centre. We show that trajectories of specific immune cells were strictly dependent on recipient age and pretransplant virus exposure, with the strongest effect seen on T CD4+ and B-cell counterparts, while donor age and transplant platforms had a minimal impact. This mirrored different kinetics of immune reconstitution in adult and paediatric patients, with major divergences in immune cell composition in late post-transplant phases, featuring better survival, relapse-free survival and cumulative incidence of pathogen-specific infections in younger patients. Altogether, these findings underpin the importance of recipient age on post-transplant immune cell recovery and define the basic dynamics of the immune reconstitution in paediatric and adult populations as a benchmark for future studies.

Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-Immune signature correlates with response.

Acute myeloid leukaemia (AML) relapse after allogeneic haematopoietic cell transplantation (allo-HCT) is often driven by immune-related mechanisms and associated with poor prognosis. Immune checkpoint inhibitors combined with hypomethylating agents (HMA) may restore or enhance the graft-versus-leukaemia effect. Still, data about using this combination regimen after allo-HCT are limited. We conducted a prospective, phase II, open-label, single-arm study in which we treated patients with haematological AML relapse after allo-HCT with HMA plus the anti-PD-1 antibody nivolumab. The response was correlated with DNA-, RNA- and protein-based single-cell technology assessments to identify biomarkers associated with therapeutic efficacy. Sixteen patients received a median number of 2 (range 1-7) nivolumab applications. The overall response rate (CR/PR) at day 42 was 25%, and another 25% of the patients achieved stable disease. The median overall survival was 15.6 months. High-parametric cytometry documented a higher frequency of activated (ICOS+ , HLA-DR+ ), low senescence (KLRG1- , CD57- ) CD8+ effector T cells in responders. We confirmed these findings in a preclinical model. Single-cell transcriptomics revealed a pro-inflammatory rewiring of the expression profile of T and myeloid cells in responders. In summary, the study indicates that the post-allo-HCT HMA/nivolumab combination induces anti-AML immune responses in selected patients and could be considered as a bridging approach to a second allo-HCT. Trial-registration: EudraCT-No. 2017-002194-18.

CMV prevention strategies in allogeneic hematopoietic cell transplantation; the role of prophylaxis and pre-emptive monitoring in the era of letermovir.

The preferred strategy for preventing CMV in at-risk populations in alloHCT has undergone a significant practice shift in recent years where the pendulum has swung from a pre-emptive approach to now offering letermovir prophylaxis to all CMV seropositive recipients. Letermovir prophylaxis has resulted in significant reductions in post-transplant clinically significant CMV infection (csCMVi) as well as other important outcomes such as CMV disease, resistant, and refractory CMV infections and nonrelapse mortality. However, prophylactic strategies are not without some limitations, namely delayed onset CMV infections, delayed CMV-specific T cell immune reconstitution, increased drug costs and limited data within pediatric populations. Thus, this review aims to provide an overview of prophylaxis and pre-emptive CMV preventative strategies, and how they are applicable in the current era of letermovir prophylaxis.

A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors.

OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.

Distinct activities of Vδ1+ T-cells upon different cytomegalovirus reactivation status after haematopoietic transplantation.

Cytomegalovirus (CMV) reactivation is the most frequent viral infectious complication correlating to non-relapse mortality after allogeneic haematopoietic cell transplantation (alloHCT). The intrinsic anti-CMV immunity has not been completely elucidated. γδ T-cells have drawn increasing attentions due to their distinct biological features and potential ability against viral infections. Previous studies reported a general association of γδ T-cells or Vδ2-negative γδ T-cells with CMV reactivation. Whereas researches for the direct responses and specific functions of γδ T subsets remain limited, especially in the scenario of alloHCT. Herein, we initially demonstrated that Vδ1+ T-cells directly and independently recognized cell-free CMV and CMV-infected target cells, and inhibited CMV replication in vitro. The anti-CMV effect of Vδ1+ T-cells was partially through TCRγδ, TLR2 and NKG2D receptor pathways. Further investigation about the anti-CMV characteristics of Vδ1+ T-cells was performed in a clinical cohort with different CMV reactivation status after alloHCT. We found that occasional CMV reactivation remarkably increased the recovery levels and stimulated the functional activity of Vδ1+ T-cells. Whereas disability of Vδ1+ T-cells was observed upon refractory CMV reactivation indicating the differential responses of Vδ1+ T-cells under different CMV reactivation status. CXCL10 and IFN-ß that were dramatically induced by occasional CMV reactivation could re-activate the deficient Vδ1+ T-cells from recipients with refractory CMV reactivation. These findings unveiled the distinct activities of Vδ1+ T-cells in anti-CMV immunity after alloHCT and may help develop novel strategies for the treatment of CMV infectious diseases.

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced-intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT.

Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n = 367), RIC (n = 687) or MAC (n = 668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively (P < 0·001) but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively, (P < 0·001). NRM was 30% (25-35), 27% (23-30) and 34% (31-38, P = 0·008), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively (P = 0·03). In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55, P < 0·001) and better OS (HR 0·72, P = 0·01). MAC was associated with higher NRM (HR 1·44, P = 0·001). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved OS. FT may be the preferred regimen for allo-HCT in MDS.

Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study.

In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3-CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.

Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre- and post-transplantation cytokine responses in stimulated whole blood.

We aimed to use a novel standardized whole-blood stimulation system to evaluate differences in the functional immune reconstitution in patients early after allogeneic haematopoietic cell transplantation (HCT). Between April and September 2018, 30 patients undergoing HCT had whole blood samples collected around day -21 (day 0 being the day of haematopoietic cell infusion) and day +28. Whole blood was transferred to TruCulture assays comprising prefilled incubation tubes with cell culture medium and a standardized stimulus. We used a panel of four stimuli (lipopolysaccharide, resiquimod, heat-killed Candida albicans and polyinosinic:polycytidylic acid) and a blank, designed to evaluate the function of critical extra- and intracellular immunological signalling pathways. For each stimulus, the cytokine response was assessed by the concentration of interferon-γ, interleukin (IL)-12p40, IL-10, IL-1ß, IL-6, IL-8, IL-10, IL-12p40, IL-17A and tumour necrosis factor-α using a multiplex Luminex assay. Pre-HCT cytokine responses were globally decreased across several different stimuli. Despite patients receiving immunosuppressive prophylaxis at the time, post-HCT cytokine responses were higher and less intercorrelated than pre-HCT responses, also after adjusting for differences in the leukocyte differential counts. For the resiquimod and heat-killed Candida albicans stimuli, we identified a cluster of patients in whom post-HCT responses were lower than average across several cytokines, indicating a possible functional immune deficiency. Our findings suggest that the standardized whole blood stimulation system can be used to reveal heterogeneity in the in vitro cytokine responses to various stimuli after HCT. Larger studies are needed to address if the functional immune reconstitution after HCT can predict the risk of infections.

Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation.

Although second allogeneic haematopoietic cell transplantation (allo-HCT2) is a therapeutic option for patients relapsing after first HCT (allo-HCT1), there is limited data on allo-HCT2 in patients with acute lymphoblastic leukaemia (ALL). We retrospectively studied 245 patients receiving allo-HCT2 as a salvage treatment for relapse following allo-HCT1 between the 2000 and 2017. The median age at allo-HCT2 was 34·6 years (range: 18-74). One hundred and one patients (41%) received sibling donor and 144 (59%) unrelated donor allo-HCT2. Acute graft-versus-host disease (GVHD) grade II-IV and III-IV occurred in 33% and 17% of the patients, respectively. The incidence of 2-year total and extensive chronic GVHD was 38% and 19%, respectively. The 2- and 5-year cumulative incidence of non-relapse mortality, relapse incidence, leukaemia-free survival, overall survival and GVHD-free, relapse-free survival (GRFS) were 24% and 26%, 56% and 62%, 20% and 12%, 30% and 14% and 12% & 7%, respectively. In multivariate analysis, factors associated with overall survival were age, time from allo-HCT1 to relapse, conditioning for allo-HCT1, Karnofsky score at allo-HCT2 and donor type for allo-HCT2. In conclusion, outcomes of allo-HCT2 in ALL patients were poor, with only 14% overall survival and 7% GRFS at 5 years with very high relapse incidence.

T memory stem cells after allogeneic haematopoietic cell transplantation: unique long-term kinetics and influence of chronic graft-versus-host disease.

T memory stem cells (TSCMs) are a subset of primitive T cells capable of both self-renewal and differentiation into all subsets of memory and effector T cells. Therefore, TSCMs may play a role in immune reconstitution and graft-versus-host disease (GVHD) in patients receiving allogeneic haematopoietic cell transplantation (HCT). We conducted a cross-sectional study to evaluate the proportions, absolute counts, phenotypes and functions of TSCMs in 152 adult patients without disease recurrence at least 12 months after undergoing HCT. CD4+ TSCMs were negatively correlated with number of months after transplantation in HCT patients that received cord blood transplantation, but not in patients that received bone marrow transplantation or peripheral blood stem cell transplantation. The proportions and absolute counts of CD4+ TSCMs and expression levels of inducible co-stimulator (ICOS) in CD8+ TSCMs were significantly higher in patients with mild and moderate/severe cGVHD compared to patients without cGVHD. These data suggested that, more than 12 months after allogeneic HCT, the kinetics of CD4+ TSCMs were dependent on the type of donor source, and further that CD4+ TSCMs and ICOS levels in CD8+ TSCMs were associated with cGVHD.

Allogeneic haematopoietic cell transplantation for adult acute myeloid leukaemia in second remission: a retrospective study of the Adult Acute Myeloid Leukaemia Working Group of the Japan Society for Haematopoietic Cell Transplantation (JSHCT).

To evaluate the outcomes and prognostic factors following allogeneic haematopoietic cell transplantation (HCT) for adult acute myeloid leukaemia (AML) in second complete remission (CR2), we retrospectively analysed the Japanese registration data of 1080 adult AML patients in CR2 who had received allogeneic HCT. The probability of overall survival and the cumulative incidence of relapse at 3 years was 66% and 19%, respectively. In multivariate analysis, older age, poor cytogenetics and shorter duration of first complete remission were significantly associated with a higher overall mortality. Our data demonstrated the significant efficacy of allogeneic HCT for adult AML in CR2.

Tocilizumab for severe cytokine-release syndrome after haploidentical donor transplantation in a patient with refractory Epstein-Barr virus-positive diffuse large B-cell lymphoma.

It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT. A 46-year-old man was diagnosed with haemophagocytic syndrome associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Salvage chemotherapy was unsuccessful; consequently, he received haplo-HCT. On day +4, he developed grade 3 CRS, subsequently high-dose corticosteroid initiated. Nevertheless, on day +6, he developed grade 4 CRS, resulting in requirement for ventilator support and multiple vasopressors. Corticosteroid could not improve severe CRS; therefore, tocilizumab was administered on day +14. Serum C-reactive protein level transiently decreased and weaned multiple vasopressors. Although CRS improved, he developed candidaemia; consequently, he died on day +34. Tocilizumab could transiently improve severe CRS after haplo-HCT. Although tocilizumab may have led to the improvement of CRS, a remaining concern is whether it inhibited the patient's ability to mount antifungal immunity, leading to their demise.

Haematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a North American multicentre collaborative study.

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.

Drug interactions and safety profiles with concomitant use of caspofungin and calcineurin inhibitors in allogeneic haematopoietic cell transplantation.

AIM: Small-scale clinical studies have reported on drug interactions between caspofungin (CPFG) and calcineurin inhibitors in healthy subjects; however, little is known about these interactions in allogeneic haematopoietic cell transplantation (allo-HCT) patients. METHODS: We retrospectively assessed the drug interactions and safety profiles in allo-HCT recipients treated concomitantly with CPFG and calcineurin inhibitors. RESULTS: Ninety-one consecutive cases were evaluated. There were no statistically significant differences in the plasma concentration/dose (C/D) ratios of tacrolimus (TAC) in 34 patients before and after co-administration with CPFG (median: 575.6-672.4, P = 0.200). In contrast, the median C/D ratio of cyclosporin A (CsA) in 16 patients was significantly elevated after co-administration with CPFG (median: 62.8-74.9, P = 0.016). There were no serious adverse effects on liver or renal function associated with the therapy. CONCLUSIONS: Our data show that CPFG did not affect the pharmacokinetics of TAC and that it could mildly increase CsA blood concentrations in allo-HCT patients.