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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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: Background: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD. Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980). Findings: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters. Interpretation: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation. Funding: MaaT Pharma.

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILC) are important barrier tissue immune regulators. They play a pivotal role in early non-specific protection against infiltrating pathogens, regulation of epithelial integrity, suppression of pro-inflammatory immune responses and shaping the intestinal microbiota. GATA2 haploinsufficiency causes an immune disorder that is characterized by bone marrow failure and (near) absence of monocytes, dendritic cells, B cells and natural killer (NK) cells. T cells develop normally, albeit at lower numbers. Here, we describe the absence of ILCs and their progenitors in blood and bone marrow of two patients with GATA2 haploinsufficiency and show that all subsets of ILCs appear after allogeneic hematopoietic stem cell transplantation, irrespective of the preparative conditioning regimen. Our data indicate that GATA2 is involved in the development of hematopoietic precursor cells (HPC) towards the ILC lineage. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILC) are important barrier tissue immune regulators. They play a pivotal role in early non-specific protection against infiltrating pathogens, regulation of epithelial integrity, suppression of pro-inflammatory immune responses and shaping the intestinal microbiota. GATA2 haploinsufficiency causes an immune disorder that is characterized by bone marrow failure and (near) absence of monocytes, dendritic cells, B cells and natural killer (NK) cells. T cells develop normally, albeit at lower numbers. Here, we describe the absence of ILCs and their progenitors in blood and bone marrow of two patients with GATA2 haploinsufficiency and show that all subsets of ILCs appear after allogeneic hematopoietic stem cell transplantation, irrespective of the preparative conditioning regimen. Our data indicate that GATA2 is involved in the development of hematopoietic precursor cells (HPC) towards the ILC lineage.

Prophylaxis with trimethoprim–sulphamethoxazole (TMP-SMZ) is recommended in Toxoplasma -seropositive allogeneic haematopoietic cell transplant (HCT) recipients to prevent reactivation, but it is associated with numerous side effects. We report our experience of a pre-emptive approach guided by a polymerase chain reaction (PCR) in patients not receiving prophylaxis. In this retrospective, single-centre experience, seropositive recipients and seronegative recipients receiving a graft from a seropositive donor were screened by PCR for the presence of Toxoplasma gondii DNA in peripheral blood until at least 6 months after transplantation. Confirmed PCR positivity triggered a pre-emptive anti- Toxoplasma therapy. Cases of Toxoplasma reactivation (using the European Society for Blood and Marrow Transplantation definitions) were compared with four controls (without reactivation), matched in time and recipient serostatus, to identify risk factors for reactivation by multivariate analysis. From November 2001 to August 2020, 1455 consecutive adult patients (59 cases and 1396 controls) were screened. The overall 1-year cumulative incidence of toxoplasmosis was 4.1% and the 1-year cumulative incidence in the seropositive recipients was 8.8%. Reactivation was associated with second transplant (OR 2.51, 95%CI 1.28–4.94, p 0.011), myeloablative conditioning (OR 2.24, 95%CI 1.17–4.41, p 0.011), total body irradiation (OR 2.29, 95%CI 1.17–4.44, p 0.010), acute graft-versus-host disease (GvHD) (OR 2.27, 95%CI 1.26–4.08, p 0.008) and use of high-dose corticosteroids (OR 2.08, 95%CI 1.14–3.78, p 0.018). In multivariate analysis only acute GvHD remained significant (adjusted OR 2.54, 95%CI 1.16–5.71, p 0.021). A PCR-based pre-emptive approach might serve as an acceptable alternative for patients unable to start with or to continue TMP-SMZ prophylaxis. Acute GvHD was identified as the single independent predictor for reactivation. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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‐1β, 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Objectives: Haploidentical haematopoietic cell transplantation (Haplo‐HCT) using peripheral blood stem cell (PBSC) grafts and post‐transplant cyclophosphamide (PTCy) is being increasingly used; however, data on immunological reconstitution (IR) are still scarce. Methods: This retrospective study evaluated T‐cell immunological reconstitution in 106 adult patients who underwent allogeneic haematopoietic cell transplantation for haematologic malignancies between 2013 and 2016. Results: At D30, while conventional T cells reached similar median counts in Haplo‐HCT recipients (n = 19) and controls (n = 87), γδ and Vδ2+ T‐cell median counts were significantly lower in Haplo‐HCT recipients and it persists at least until D360 for Vδ2+ T cells. PTCy induces a significant reduction in early γδ and Vδ2+ T‐cell proliferation at D 7. At one year, the rate of increase in Epstein–Barr virus (EBV) viral load was significantly higher in Haplo‐HCT recipients as compared to controls (61% versus 34%, P = 0.02). In multivariate analysis, a higher γδ T‐cell count (> 4.63 μL−1) at D30 was the only independent parameter significantly associated with a reduced risk of increase in EBV viral load (RR 0.34; 95% CI, 0.15–0.76, P = 0.009). Conclusion: Immunological reconstitution of γδ T cells is significantly delayed after Haplo‐HCT using PTCy and low‐dose ATG and is associated with an increased risk of increase in EBV viral load. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Keywords: B-acute lymphoblastic leukaemia; chimeric antigen receptor T cell; allogeneic haematopoietic cell transplantation EN B-acute lymphoblastic leukaemia chimeric antigen receptor T cell allogeneic haematopoietic cell transplantation 21 23 3 03/31/20 20200401 NES 200401 In this issue of the I British Journal of Haematology, i Zhang I et al. i ([19]) from Beijing Boren Hospital describe the outcomes of 52 patients with B-acute lymphoblastic leukaemia (B-ALL) who underwent consolidative allogeneic haematopoietic cell transplantation (allo-HCT) after achieving a complete remission (CR) following chimaeric antigen receptor T-cell (CAR T) therapy. In the majority of the cases, disease relapse happened within a year of CAR T therapy and loss of CD19 was detected despite persistent B-cell aplasia (Grupp I et al. i , [2]). In the study by Park I et al. i ([12]), all patients with MRD-positive CR after CAR T therapy had disease relapse within a year. [Extracted from the article]

Abstract Background Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). Methods In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen–matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively. Results The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p < 0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p < 0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p < 0.001) and extensive chronic GVHD (HR = 0.46, p < 0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality. Conclusions The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation. Highlights • Decreased risk of chronic graft-versus-host disease for patients treated with anti-thymocyte globulin (ATG). • Increased risk of relapse associated with the use of ATG. • No impact on survival associated with the use of ATG. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Letermovir for cytomegalovirus (CMV) prophylaxis in allogeneic haematopoietic cell transplant (HCT) recipients has decreased anti-CMV therapy use. Contrary to letermovir, anti-CMV antivirals are also active against human herpesvirus-6 (HHV-6). We assessed changes in HHV-6 epidemiology in the post-letermovir era. We conducted a retrospective cohort study of CMV-seropositive allogeneic HCT recipients comparing time periods before and after routine use of prophylactic letermovir. HHV-6 testing was at the discretion of clinicians. We computed the cumulative incidence of broad-spectrum antiviral initiation (foscarnet, (val)ganciclovir, and/or cidofovir), HHV-6 testing, and HHV-6 detection in blood and cerebrospinal fluid within 100 days after HCT. We used Cox proportional-hazards models with stabilized inverse probability of treatment weights to compare outcomes between cohorts balanced for baseline factors. We analysed 738 patients, 376 in the pre-letermovir and 362 in the post-letermovir cohort. Broad-spectrum antiviral initiation incidence decreased from 65% (95% CI, 60–70%) pre-letermovir to 21% (95% CI, 17–25%) post-letermovir. The cumulative incidence of HHV-6 testing (17% [95% CI, 13–21%] pre-letermovir versus 13% [95% CI, 10–16%] post-letermovir), detection (3% [95% CI, 1–5%] in both cohorts), and HHV-6 encephalitis (0.5% [95% CI, 0.1–1.8%] pre-letermovir and 0.6% [95% CI, 0.1–1.9%] post-letermovir) were similar between cohorts. First HHV-6 detection occurred at a median of 37 days (interquartile range, 18–58) in the pre-letermovir cohort and 27 (interquartile range, 25–34) in the post-letermovir cohort. In a weighted model, there was no association between the pre-versus post-letermovir cohort and HHV-6 detection (adjusted hazard ratio, 1.08; 95% CI, 0.44–2.62). : Despite a large decrease in broad-spectrum antivirals after the introduction of letermovir prophylaxis in CMV-seropositive allogeneic HCT recipients, there was no evidence for increased clinically detected HHV-6 reactivation and disease. [ABSTRACT FROM AUTHOR]

Chronic graft versus host disease (cGVHD) is a complication of allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to clinically characterize childhood cutaneous cGVHD. A retrospective study of children treated with HSCT at 2 tertiary medical centres in Israel between 2011 and 2014 was performed. A total of 112 children were included. Cutaneous cGVHD developed in 18% of subjects. Risk factors were older age, HSCT from peripheral blood and acute lymphoblastic leukaemia. The eruption was lichenoid in 90% of subjects, of whom onethird progressed to sclerosis. Topical treatments were usually sufficient in localized disease. Widespread eruption necessitated phototherapy, extracorporeal photopheresis and/or systemic immunosuppressants. Patients presenting with palmoplantar keratoderma, developed sclerosis. To the best of our knowledge, this is the first study describing childhood cutaneous cGVHD. Lichenoid eruption is the most common cutaneous pattern of cGVHD in children. Sclerotic changes may be associated with prior keratoderma. cGVHD poses a therapeutic challenge and better treatments should be sought. [ABSTRACT FROM AUTHOR]

Objectives:Although decreased thyroid function is negatively correlated with clinical outcomes in critically ill patients, its role in allogeneic haematopoietic cell transplantation (allo-HCT) has not been sufficiently described. Methods:The associations between pre-conditioning thyroid hormone concentrations and transplant-related complications in 474 adult patients with haematologic malignancies who underwent myeloablative allo-HCT were assessed. Results:A receiver-operating characteristic curve showed that the baseline serum-free triiodothyronine 3 (FT3) level had an excellent predictive value for non-relapse mortality (NRM) within 100 days in sibling HCT with an area under the curve of 0.73 [95% confidence interval (CI), 0.64–0.82]. With a cut-off value of 4.7 pmol/l, the sensitivity and specificity for early NRM were 68% and 73%, respectively. The cumulative incidences of early NRM within 100 days after sibling HCT were 14% (95% CI, 10–18%) in the low FT3 group and 6% (95% CI, 4–8%) in the high-FT3 group (p = 0.033). In multivariate analysis, a lower FT3 level was significantly associated with high early NRM (HR = 3.19, 95% CI, 1.13–9.03,p = 0.029). The difference was also significant at 3 years after HCT (24% vs. 14%,p = 0.046). Recipients with lower FT3 levels also had a trend towards a lower OS at 3 years after HCT (66% vs. 72%,p = 0.235), although the difference did not reach statistical significance. Conclusion:A low FT3 level before conditioning may be a useful predictive biomarker for higher early NRM among patients undergoing myeloablative sibling transplantation. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years. In this review, we describe the indications for allografting adult ALL patients in first complete remission (CR1). Role of minimal residual disease (MRD) in optimising HCT for ALL is delineated. We also discuss how alternative donors, haploidentical and cord blood and reduced intensity conditioning make allografts more accessible to patients with high-risk ALL. Recent data on use of monoclonal antibodies and chimeric antigen receptor (CAR)-modified T cells in adult ALL patients are also reviewed. [ABSTRACT FROM AUTHOR]

To develop effective strategies to preserve and/or restore gut microbiota composition during the course of allo-HCT and improve patient outcome, it is therefore of the utmost importance to understand the fluctuation of the gut microbiota. Overall, sequential daily analysis of the gut microbiota reveals that the beneficial gut bacterial microbiota were already impaired before allo-HCT and that the stability of the intestinal microbiota is critically involved in the outcome of allo-HCT. [Extracted from the article]

Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia ( AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30-40% of adults and 60-70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed. [ABSTRACT FROM AUTHOR]

The prognostic significance of molecular mutations (FLT3-ITD, NPM1, and CEBPA mutations) was examined in patients with normal-karyotype acute myeloid leukaemia (NK-AML) after allogeneic haematopoietic cell transplantation (HCT). In total, 115 patients received allogeneic HCT for NK-AML and were evaluated for FLT3-ITD, NPM1, and CEBPA mutations in diagnostic samples and for long-term outcomes following HCT, retrospectively. The prevalences of FLT3-ITD(pos), NPM1 (mut), and CEBPA (dm) (double mutations) were 32.2, 43.5, and 24.6 %, respectively. The triple-negative group (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) showed a similar transplant outcome to those in the favourable European LeukemiaNet (ELN) risk group for overall survival (OS) (60.9 vs. 63.7 %; p = 0.810), but a more favourable OS than others in the intermediate-I risk group (40.0 %; p = 0.034). Also, the triple-negative group showed a similar relapse rate at 5 years compared with those in the favourable risk group (9.7 vs. 15.5 %; p = 0.499), but a lower rate of relapse than the others in the intermediate-I risk group (15.5 vs. 48.6 %; p = 0.004). The 5-year relapse incidences were 4.0 % (NPM1 (mut)/FLT3-ITD(neg)), 14.7 % (CEBPA (dm)), 15.5 % (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)), 39.1 % (NPM1 (mut)/FLT3-ITD(pos)/non-CEBPA (dm)), and 66.7 % (NPM1 (wild)/FLT3-ITD(pos)/non-CEBPA (dm)). Thus, the triple-negative (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) group showed favourable long-term outcomes after allogeneic HCT in NK-AML, similar to those of the favourable risk group by the ELN risk classification. [ABSTRACT FROM AUTHOR]

The article presents a study which examined through quantitative analysis the CBFB-MYH11 log-reduction as minimal residual disease (MRD) after allogeneic haematopoietic cell transplantation (allo-HCT). Also cited are the effectiveness of post-transplant CBFB-MYH11 monitoring as MRD in predicting relapse after allo-HCT in adult patients with inv(16) acute myeloid leukemia (AML), as well as the indictions for allo-HCT including haematological relapse after chemotherapy.

The optimum intensity of conditioning therapy in patients aged 40-60 years with AML and myelodysplastic syndrome (MDS) undergoing allogeneic haematopoietic cell transplantation (alloHCT) remains uncertain. We compared outcomes of reduced intensity conditioning (RIC) and conventional intensity conditioning (CIC) in 101consecutive patients (CIC, 62; RIC, 39) with AML and MDS aged 40-60 years undergoing alloHCT from 2002 to 2008 at our centre. The median age, unrelated transplants and co-morbidity index were higher in the RIC group. Median OS and EFS were 31.0 months (95% confidence interval (CI): 12.8-59.3) and 20.7 months (95% CI: 11.0-30.4), respectively, with no significant difference between the two cohorts. The 3-year treatment-related mortality (TRM) and relapse were 28% (95% CI: 21-39) and 25% (95% CI: 17-36), respectively, with no significant difference between the two cohorts. No difference in OS, EFS, TRM or relapse was observed between the two cohorts in the multivariate model. Only disease risk was significantly associated with OS (Hazard ratio (HR): 1.85, CI: 1.01-3.45), EFS (HR: 1.73, 95% CI: 1.00-3.10) and cumulative relapse (HR: 3.24, 95% CI: 1.08-10.12). Disease biology rather than intensity of conditioning regimen seems to determine outcomes of alloHCT in patients aged 40-60 years with AML/MDS. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed transfusion requirements within the first 100 d among allogeneic haematopoietic cell transplantation (HCT) recipients with haematological malignancies given either myeloablative ( n = 1353) or nonmyeloablative conditioning ( n = 503). We confirmed that myeloablative recipients required more platelet and red blood cell (RBC) transfusions than nonmyeloablative recipients ( P < 0·0001 for both). Myeloablative patients given peripheral blood stem cells required less platelet transfusions ( P < 0·0001) than those given marrow while RBC transfusion requirements did not differ significantly. Subsequent analyses were restricted to nonmyeloablative recipients. Platelet and RBC transfusions were less frequent among related compared to unrelated recipients ( P < 0·0001 for both), with comparable median numbers of transfused units. Major/bidirectionally ABO-mismatched recipients required more RBC transfusions than ABO-matched recipients ( P = 0·006). Rates of graft rejection/failure, grades II–IV acute and chronic graft- versus-host-disease (GVHD), 2-year relapse, 3-year survivals and non-relapse mortality were comparable among ABO-matched, minor-mismatched, and major/bidirectionally mismatched recipients ( P = 0·93, 0·72, 0·57, 0·36, 0·17 and 0·79, respectively). Times to disappearance of anti-donor IgG and IgM isohemagglutinins among major/bidirectionally ABO-mismatched recipients were affected by magnitude of pre-HCT titres ( P < 0·001 for both) but not GVHD ( P = 0·71 and 0·78, respectively). In conclusion, nonmyeloablative recipients required fewer platelet and RBC transfusions and among them, both unrelated and major/bidirectionally ABO-mismatched recipients required more RBC transfusions. ABO incompatibility did not affect nonmyeloablative HCT outcomes. [ABSTRACT FROM AUTHOR]

Chronic graft- versus-host disease (cGVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT). It is the leading cause of non-relapse mortality in transplant survivors and has a significant impact upon their functional status and quality of life. Despite significant advances being made in the field of HCT over the past 25 years, there has been little change in the incidence, morbidity and mortality of cGVHD. This is partly because of a lack of understanding about the pathogenesis of the disorder but also because a lack of well validated grading systems and outcome measures has hindered clinical research. Strategies for prophylaxis have largely been unsuccessful and may compromise the graft- versus-leukaemia (GVL) effect. Standard primary treatment remains a combination of corticosteroids and calcineurin inhibitors. There is no standard therapy for those who fail to respond to corticosteroids. Many agents have been studied but there is an urgent need for systematic research to compare the efficacy of different approaches. Infection is the leading cause of death among patients with cGVHD so antimicrobial prophylaxis is mandatory. A multidisciplinary approach to the care of patients with cGVHD is essential to adequately address its effects on both physical and psychological functioning. [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic haematopoietic cell transplantation (allo-HCT) provides effective therapy for patients with various haematological malignancies. In multiple myeloma (MM) this approach can induce response rates in 35–75% of patients. However, the outcome is hampered by high rates of treatment-related mortality (TRM). Reduced intensity conditioning to lower TRM has been successfully applied. The fact that previous clinical reports have documented graft-versus-myeloma (GVM) activity without graft-versus-host disease (GVHD) suggests that at least two distinct immunocompetent cell populations mediating GVHD and/or GVM may exist. Further characterization of effectors after allo-HCT and their targets may help to clarify the immune response that mediates the GVM effect. This review considers the clinical results with myeloablative and reduced intensity conditioning prior to allo-HCT for MM, with emphasis on attempts to prevent GVHD while preserving the GVM effect. Strategies including donor lymphocyte infusions as part of the allogeneic protocol and antigenic targets for GVM effect are reviewed. [Copyright &y& Elsevier]

To assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT). This is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4–6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies. The cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4–439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7–21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19–35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1–4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97–11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2–29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination. A significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population. [ABSTRACT FROM AUTHOR]

Infections contribute greatly to the morbidity and mortality of allogeneic haematopoietic cell transplantation (HCT), an important part of this is due to viral infections, some of which are respiratory viruses (Dignan I et al. i , [2]; Hill I et al i , [4]). A common clinical problem is, for example, the patient with chronic GvHD acquiring a respiratory viral infection, this triggering GvHD of the lung, e.g. obstructive bronchiolitis syndrome, which may ultimately lead to death of the patient. We do not know however, how patients were selected for immediate HCT as compared to deferred HCT, hence, other decision-guiding patient-related characteristics might have significantly contributed to the difference observed. [Extracted from the article]

Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory., Clinical Presentation: We report for the first time two cases of YNS associated with multiple myeloma relapsing after non-myeloablative haematopoietic cell transplantation (HCT). In these two cases, onset or worsening of YNS symptoms followed graft-versus-host disease (GvHD) manifestations., Intervention: Corticosteroids given to treat GvHD also improved YNS manifestations., Conclusion: YNS after HCT might be a microvascular manifestation of endothelial GvHD and corticosteroids might be an effective treatment.