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This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults. [ABSTRACT FROM AUTHOR]

Summary: European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo‐HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia‐free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse‐plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2‐year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo‐HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group. [ABSTRACT FROM AUTHOR]

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]

Graft‐versus‐host disease (GVHD) is a complication of allogeneic haematopoietic cell transplantation. Endothelial injury is crucial as pathophysiological substrate for GVHD. GVHD first‐line treatment is high‐dose corticosteroids, although some patients are steroid‐refractory. Through the present study, we compared the endothelial proteomic profiles in response to serum from steroid‐refractory acute GVHD (SR‐aGVHD) and steroid‐sensitive acute GVHD (SS‐aGVHD) patients. Blood samples from SR‐aGVHD (n = 4) and SS‐aGVHD (n = 8) patients were collected at aGVHD diagnosis. Endothelial cell cultures were exposed (48 h) to patients' serum. Protein extraction and proteomic analysis were performed. Differences were statistically evaluated by multivariate analysis. Forty‐four proteins contributed to separate all samples into the two study groups, among which 15 participated significantly (p < 0.05), 10 exhibiting a fold change >1.2. Differentially expressed proteins were mainly associated with oxidative phosphorylation (Cytochrome C oxidase subunit 6B1, CX6B1), inflammation and angiogenesis (Apolipoprotein D, APOD), cell survival (Rapamycin‐insensitive companion of mTOR, RICTR), and oxidative stress (Riboflavin kinase, RIFK). This pilot study used a novel approach to distinguish the aGVHD response to steroid treatment. The proteins differentially expressed could constitute potential biomarkers for steroid‐treatment response. These findings signify a step forward to identify the mechanisms of response to steroids, of high clinical relevance considering the SR‐aGVHD elevated mortality. [ABSTRACT FROM AUTHOR]

Background: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high‐risk acute lymphoblastic leukemia (ALL) lacking a matched donor. Methods: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft‐vs‐host disease (GVHD) prophylaxis in 2010–2020. Results: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19–73) and 38 (18–75) years, respectively (p =.51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T‐cell depletion (anti‐thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p <.0001). Neutrophil (absolute neutrophil count >0.5 × 109/L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81–2.62; p =.21) and HR = 0.81 (95% CI, 0.52–1.28, p =.38), respectively. HRs for leukemia‐free survival, overall survival, and GVHD‐free, relapse‐free survival were respectively, HR = 1.05 (95% CI, 0.73–1.50, p =.8), HR = 1.17 (95% CI, 0.77–1.76, p =.46), and HR = 1.07 (95% CI, 0.78–1.46, p =.7) for haplo compared to MMUD. Acute (a)GVHD grade 2–4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08–2.76, p =.023), whereas aGVHD grade 3–4 and chronic GVHD did not differ significantly between the two transplant groups. Conclusion: Outcomes of MMUD and haplo transplants with PTCy‐based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants. The outcomes of mismatch unrelated and haploidentical transplants in patients with acute lymphocytic leukemia (ALL) in complete remission are similar. The donor pool for patients with ALL who are in need of allogeneic transplantation and do not have a human leukocyte antigen‐compatible donor is, therefore, enlarged. [ABSTRACT FROM AUTHOR]

BACKGROUND: The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo‐SCT) for this patient group, although this has not been studied in a large cohort. METHODS: A total of 780 patients with AML in first complete remission, with either intermediate‐ or adverse‐risk cytogenetics, whose TP53 mutation status was reported, were included in this study from the European Society for Blood and Marrow Transplantation. RESULTS: Two‐year overall survival (OS) was impaired in patients (n = 179) with evidence of a TP53 mutation at diagnosis (35.1%; 95% confidence interval [CI], 26.7–43.7) as compared to the cohort without (n = 601) (64%; 95% CI, 59.1–68.4; P =.001). In patients with mutant TP53 AML with no evidence of either chromosome 17p loss (17p–) and/or complex karyotype (CK) (n = 53, 29.6%), 2‐year OS was 65.2% (95% CI, 48.4–77.6). This was not significantly different to patients without TP53 mutations. In patients with mutant TP53 AML with either 17p– and/or CK (n = 126, 70.4%), the OS was lower (24.6%; 95% CI, 16.2–34; P =.001). CONCLUSIONS: In summary, the adverse prognostic effect of TP53 mutations in AML following an allo‐SCT is not evident in patients with neither co‐occurring 17p– and/or CK, and these data inform decisions regarding allo‐SCT in patients with TP53 mutant AML. [ABSTRACT FROM AUTHOR]

Patients were transplanted with a median time to allo-HCT of 15.1 months (IQR, 9.8-27.9) for CEL, NOS patients, and 22.2 months (IQR, 11.5-55.8; I p i = 0.01) for HES. Helbig et al. reported on 10 patients with CEL, NOS with a median age of 62 (23-73 years), frequently with an aggressive clinical course, five of whom developed acute transformation within two years from the time of diagnosis.6 Here, only one patient in the chronic phase successfully underwent allo-SCT. Keywords: allogeneic stem cell transplant; chronic eosinophilic leukaemia; conditioning; hypereosinophilic syndrome; non-relapse mortality EN allogeneic stem cell transplant chronic eosinophilic leukaemia conditioning hypereosinophilic syndrome non-relapse mortality 209 213 5 06/27/22 20220701 NES 220701 Hypereosinophilic syndrome (HES) and chronic eosinophilic leukaemia (CEL), not otherwise specified (NOS) are rare haematological disorders.1 Allogeneic haematopoietic cell transplantation (allo-HCT) has been reported in single case reports or small case series only for both refractory HES or CEL, NOS and outcomes remain ill-defined.1-3 HES normally demonstrates a male predominance, likely underrecognized, with a variable clinical course. [Extracted from the article]

The potential role of active CMV infection in promoting acute Graft‐versus‐Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real‐time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%‐52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%‐50.1%), and of grade II‐IV aGvHD, 30.7 (95% CI, 24.9%‐36.4%). Overall, development of CMV DNAemia at any level resulted in an increased risk of subsequent all grade (HR, 1.38; 95% CI, 1.08 ‐ 1.76; P =.009) or grade II‐IV (HR, 1.58; 95% CI, 1.22 ‐ 2.06; P =.001) aGvHD. The increased risk of aGvHD linked to prior occurrence of CMV DNAemia was similar to the above when only clinically significant episodes were considered for the analyses (HR for all grade aGvHD, 1.48; 95% CI, 1.13 ‐ 1.91; P =.041, and HR for grade II‐IV aGvHD, 1.53; 95% CI. 1.13‐1.81; P =.04). The CMV DNA doubling time in blood was comparable overall in episodes of CMV DNAemia whether followed by aGvHD or not. Whether CMV replication is a surrogate risk marker of aGvHD or it is causally involved is an important question to be addressed in future experimental research. [ABSTRACT FROM AUTHOR]

Background: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals.Study Design and Methods: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations.Results: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01).Conclusion: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule.Study Design and Methods: Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures.Results: Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively.Conclusion: Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe. [ABSTRACT FROM AUTHOR]

Limited data has been published on the treatment results in patients with light-chain deposition disease ( LCDD). Whenever possible, high-dose melphalan followed by autologous stem cell transplantation ( ASCT) has been the first treatment option, achieving somehow better results than conventional therapy. However, and based on the promising results obtained by treating patients with light-chain amyloidosis with bortezomib/dexamethasone, new treatment options appear in LCDD. Herein, we describe three patients with LCDD treated with bortezomib/dexamethasone followed by high-dose melphalan and autologous transplantation. We believe that this new approach should be the treatment of choice in this disease. In addition, those patients achieving hematologic complete response after ASCT could benefit from a kidney transplant if the renal impairment requiring dialysis persists. [ABSTRACT FROM AUTHOR]

Aguilar-Guisado M, Jiménez-Jambrina M, Espigado I, Rovira M, Martino R, Oriol A, Borrell N, Ruiz I, Martín-Dávila P, de la Cámara R, Salavert M, de la Torre J, Cisneros JM, on behalf of Spanish Network for Research in Infectious Diseases. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. Clin Transplant 2011: 25: E629-E638. © 2011 John Wiley & Sons A/S. Abstract: Pneumonia is a common cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) but updated and prospective information is partial. The aim of this nationwide prospective study is to determine the current epidemiology, etiology, and outcome of pneumonia in allo-HSCT recipients. From September-2003 to November-2005, 112 episodes in 427 consecutive allo-HSCT recipients were included (incidence 52.2 per 100 allo-HSCT/yr), and 72 of them (64.3%) were microbiologically defined pneumonia. Bacterial pneumonia (44.4%) was more frequent than fungal (29.2%) and viral pneumonia (19.4%). The most frequent microorganisms in each group were : Escherichia coli (n = 7, 8.9%), Streptococcus pneumoniae (n = 4, 5.0%), cytomegalovirus (n = 12, 15.4%), and Aspergillus spp. (n = 12, 15.4%). The development of pneumonia and chronic graft-versus-host disease (GVHD) was associated with increased mortality after allo-HSCT, and the probability of survival was significantly lower in patients that had at least one pneumonia episode (p < 0.01). Pneumonia development in the first 100 d after transplantation, fungal etiology, GVHD, acute respiratory failure, and septic shock were associated with increased mortality after pneumonia. Our results show that pneumonia remains a frequent infectious complication after allo-HSCT, contributing to significant mortality, and provide a large current experience with the incidence, etiology and outcome of pneumonia in these patients. [ABSTRACT FROM AUTHOR]

A 40-year-old man with severe chronic idiopathic CD4+ lymphocytopenia complicated with opportunistic infections was successfully treated with non-myeloablative allogeneic hematopoietic stem cell transplantation. After conditioning with fludarabine plus low dose of total-body irradiation, CD34+ peripheral blood stem cells obtained by leukapheresis from his HLA-identical sister were infused. T cell and myeloid complete chimerism was achieved at day +28 and remained stable during the follow-up period. The patient did not develop infectious complications during the procedure. At 35 months of follow-up, his CD4+ T cell count was 1019 cells per microliter. Non-myeloablative allogeneic hematopoietic stem cell transplantation should be considered a treatment option for patients with severe forms of idiopathic CD4+ lymphocytopenia. [ABSTRACT FROM AUTHOR]

A 44-yr-old man with IgG-lambda multiple myeloma reached a complete response after induction chemotherapy and autologous stem cell transplantation and maintenance therapy with interferon α2b and prednisone 4 yr later, he presented an increase in the M-protein plus extramedullary myeloma involvement with sacrum and clivus plasmacytomas. Treatment with bortezomib, cyclophosphamide and dexamethasone plus local radiotherapy was initiated. The patient developed a bilateral humeral pathological fracture. Surgical osteosynthesis of both humeri was performed with no immediate complications. Two months later, he developed a prominent swelling in both deltoid areas with fever and high serum LDH levels. X-ray examination showed a displacement of bone fragments of both humeri. Humerus CT scan showed a bilateral fracture in proximal diaphysis with posterior displacement. A magnetic resonance of right scapular region revealed a very extensive infiltration originated in the humerus. A fine-needle punction showed a diffuse plasmablastic infiltration. This case illustrates an atypical presentation of extramedullary myeloma with extensive soft-tissue involvement, originated at the fractured lytic lesions, which was likely triggered by bone surgery. This direct mechanism of myeloma spread has been observed in experimental myeloma mouse models. [ABSTRACT FROM AUTHOR]

The case of a 52-years-old man with generalized acquired cutis laxa associated with IgG-lambda monoclonal gammopathy and nephrotic syndrome with renal failure (due to fibrillar glomerulopathy resulting from IgG deposition) is reported. A peripheral blood autologous stem cell transplant was planned, but the procedure was complicated by severe pulmonary hemorrhage during stem cells mobilization with granulocyte colony-stimulating factor (G-CSF). Treatment with bortezomib and dexamethasome was subsequently started and a complete hematological response was achieved. Finally, the complete hematological response with the disappearance of the toxic M-protein allows the possibility of a long-term benefit with a kidney transplant followed by an autologous bone marrow transplant. [ABSTRACT FROM AUTHOR]

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin ( n = 51), microbiological ( n = 26) or clinical ( n = 5) documented infection and non-infectious febrile episodes ( n = 10). On first day of fever, mean (±SD) PCT level was 0·3 ng/ml (0·2) in neutropenic fever of unknown origin, 0·5 ng/ml (0·7) in microbiologically confirmed infections, 0·2 ng/ml (0·2) in clinically documented infections and 1·7 (4·2) in non-infectious fever ( P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10·1 ng/ml (6·7)] than all remaining groups ( P = 0·027; Kruskal–Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis. [ABSTRACT FROM AUTHOR]

Summary. We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0·0001; OR 4·6) and having received steroid prophylaxis for GvHD (P = 0·04; OR 2·1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0·0001; OR 5·6), non-early disease phase (P = 0·0001; OR 1·9), steroid prophylaxis (P = 0·02; OR 1·4), moderate-to-severe GvHD (P = 0·01; OR 1·6) and cytomegalovirus infection post transplant (P = 0·001; OR 1·8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors. [ABSTRACT FROM AUTHOR]

Although splenic rupture is a recognized complication of primary amyloidosis, very few cases have been reported in the context of stem cell transplantation. A patient with systemic primary amyloidosis with renal and cardiac involvement and factor X deficiency, who developed a splenic rupture 24 h after the peripheral blood stem cells infusion during autologous transplantation, is described. This complication has been reported during stem cell mobilization and after post-transplant hematopoietic recovery, but we have not found a previous report of splenic rupture in the immediate postinfusion period. This case illustrates that splenic rupture can occur at any time during the transplant procedure. Need for close monitoring, particularly in patients with factor X deficiency after receiving granulocyte colony stimulating factor, two recently recognized risk factors for splenic hemorrhage, is highlighted. [ABSTRACT FROM AUTHOR]