Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.

Peracetic acid sterilized tendon and ligament allografts for knee reconstruction : For anterior cruciate ligament (ACL), posterior cruciate ligament (PCL) and complex knee surgery.

BACKGROUND: The use of allografts and autografts has been met with mixed views on whether allografts are a suitable alternative to autografts. QUESTION: We aimed to investigate if chemically sterilized allografts show similar rerupture rates to those reported in the literature for allografts and autografts in anterior (ACL) and posterior cruciate ligaments (PCL) and complex knee surgery. MATERIALS AND METHODS: Retrospective data on knee reconstructions performed between 2011 and 2015 with tendon/ligamnet allografts sterilized with peracetic acid were collected in the form of a questionnaire. The inclusion criteria of 2 years for each patient were met by 38 patients, representing 22 ACL reconstructions, 5 PCL reconstructions, 3 OTHER surgeries, including the Larson technique and medial patellofemoral ligament (MPFL) reconstruction and 8 COMPLEX surgeries. The main endpoints were rerupture and complication rate. Secondary endpoints included stability of the knee (Lachman test, Pivot shift test) and the range of motion. RESULTS: The rerupture rate was 7.9% (3 grafts). Reruptures only occurred in the ACL group. No reruptures were observed in the PCL, OTHER and COMPLEX surgery groups. Stability improved significantly after surgery and the range of motion returned to values similar to that of healthy knees. CONCLUSIONS: Tendon allografts sterilized with peracetic acid show promising low rerupture rates and good clinical scores and the results are comparable to the literature on autografts and other allografts.

Comparing between HLA-matched sibling donor allogenic HSCT and non-sibling matched related donor allogenic HSCT outcome in pediatric patients; single center retrospective study.

BACKGROUND: Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non-sibling matched related donors (NS-MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). METHODS: We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non-sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). RESULTS: A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS-MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS-MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS-MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431-3525). CONCLUSIONS: This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non-sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated.

The effectiveness of acellular nerve allografts compared to autografts in animal models: A systematic review and meta-analysis.

BACKGROUND: Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. OBJECTIVE: To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. MATERIAL AND METHODS: PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. RESULTS: Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. CONCLUSION: Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, > 1-2cm) nerve gaps is preferred over an allograft in long (> 2cm) nerve gaps.

The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping.

Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a challenging problem, and the impact on the risk of overall mortality (OM) and non-relapse mortality (NRM) in patients following allo-HSCT is still controversial. Utilizing the evidence mapping method, we aimed to assess the effect of CMV infection on outcomes of patients post-transplantation and identify research gaps through systematic reviews (SRs) and clinical studies. PubMed, EMBASE, Web of Science, and Cochrane library databases were searched from inception until 5 July 2022 to identify relevant literature. After systematic literature screening and data extraction, evidence mapping of the effects of CMV reactivation on patients post-allo-HSCT was conducted. Three SRs and 22 clinical studies were included. In one SR, CMV reactivation was associated with an increased risk of mortality (HR 1.46; 95% CI, 1.24-1.72; P ≤ 0.001). In two SRs, CMV reactivation was associated with NRM. One SR reported CMV reactivation was potentially associated with significant protection against relapse in patients with acute myelocytic leukemia (AML), but no significant correlation with graft-versus-host disease (GVHD) was found. Lastly, in one SR CMV reactivation significantly increased the risk of invasive fungal disease (IFD). Most clinical articles reported that CMV reactivation increased the risk of renal dysfunction, poor graft function, re-hospitalization, and bacterial infections. CMV reactivation following allo-HSCT is associated with an increased risk of OM, NRM, IFD, and renal dysfunction, as well as a reduced risk of relapse in patients with AML.

Short-Term Outcomes After Bipolar Osteochondral Allograft Transplantation (OCAT) in the Ankle.

Treatment options for symptomatic cartilage loss in the ankle are not consistently effective. This study documents initial outcomes for patients undergoing bipolar OCAT in the ankle after advances in tissue preservation, transplantation techniques, and patient management strategies were implemented. Patients were prospectively enrolled into a registry designed to follow outcomes after OCAT in the ankle. Fourteen patients were included for analyses (12 primary OCAT, 2 revision OCAT). Four patients underwent Bipolar OCAT (tibia, talus) and 10 Bipolar+ OCAT (tibia, talus, fibula). Short-term (median follow-up 43, range 13-73 months) success was documented for 13 patients. Radiographic assessments indicated OCA integration and maintenance of joint space in 12 patients. Statistically significant (p < .030) and clinically meaningful improvements in AAOS and VAS pain scores were noted at 3 months, 6 months, 1 year, and 2 years following OCA transplantation when compared to preoperative measures. For patients that were nonadherent to postoperative restriction and rehabilitation protocols, all 1-year postoperative PROs were significantly lower (p < .050) than for patients who were adherent. The successful outcomes documented in 13 of 14 patients in conjunction with significant and clinically meaningful improvements in patient-reported measures of pain and function support OCA transplantation as an appropriate treatment option in indicated patients. These improvements in outcomes were associated with advances in OCA preservation, preimplantation treatment, transplantation techniques, and patient management strategies, suggesting this shift in practice be considered for OCA transplantation in the ankle.

Allogeneic hematopoetic stem cell transplant for patients with refractory T-Cell lymphomas.

OBJECTIVE: Allogeneic stem cell transplantation (allo-SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory-T-NHL (ref-NHL) and Chemosensitive-T-NHL (CS-T-NHL). MATERIALS AND METHODS: We retrospectively reviewed the records of 26 ref-NHL and 29 CS-T-NHL consecutive patients who underwent allo-SCT at our center and compared the transplant outcomes between the groups. RESULTS: All patients were heavily pretreated with 27% of patients relapsing post-auto-SCT and two patients in the ref-T-NHL post-allo-SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref-TNHL and 19% in CS-TNHL (p = .33), with non-relapse mortality rates of 28% and 22%, respectively (p = .52). Female patients and those with a previous auto-SCT had lower relapse incidence (p = .045, p = .003). The 3-year overall survival was 39% in Ref-TNHL and 56% in CS-TNHL (p = .15). Trends for improved progression-free survival (PFS) and graft-versus-host disease relapse-free survival (GRFS) were observed in the CS-TNHL group (PFS: 60% vs. 30%, p = .075; GRFS: 38% vs. 21%, p = .1). CONCLUSION: Acknowledging the retrospective nature of our study, our results indicate that allo-SCT has a curative potential in patients with T-NHL even in refractory status.

Dehydrated human amnion/chorion membrane allograft with spongy layer to significantly improve the outcome of chronic non-healing wounds.

We investigated the healing effect of a new dehydrated amnion/chorion membrane with a spongy layer over a 30-month period in 32 patients with 53 chronic non-healing wounds of different aetiologies. Wounds with <40% surface reduction after 4 weeks of best wound treatment underwent weekly allograft application by a certified wound specialist based on national guidelines and a standardised protocol until complete healing or definite treatment interruption. The main outcome measure was the percentage of wound surface reduction from baseline calculated using digital planimetry follow-up photographs. Overall, 38 (71.7%) wounds presented a favourable outcome (70%-100% area reduction), with 35 (66%) completely healing over a median time of 77 days (range 29-350 days). Favourable outcomes were observed in 75% of traumatic wounds, surgical wounds, venous leg ulcers and pressure injuries, as well as in 50% of ischaemic wounds. Wounds being present <12 months were significantly more likely to have a favourable outcome than more long-standing wounds (χ2 = 7.799; p = 0.005; OR = 3.378; 95% CI, 1.410-8.092). Thus, treatment with dehydrated amnion/chorion membrane with a spongy layer improves the outcome of non-healing wounds of different aetiologies and, therefore, has to be considered early in the management of refractory wounds.

Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy.

ABSTRACT: Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

The effect of sterilization and storage on the viscoelastic properties of human tendon allografts - Continued: Storage for 0 to 4 months.

The role of donor-derived tendons, also known as allografts, in anterior cruciate ligament replacement surgeries is steadily increasing. Before surgery, temporary storage and, in most cases, sterilization are essential. It is, thus, crucial to determine how these procedures alter the grafts' biomechanical properties. The purpose of this research was to analyze the effect of different sterilization methods (native, frozen, frozen + 21 kGy gamma irradiation, frozen + 21 kGy electron beam irradiation) and storage durations (0 to 4 months) on the deformation and creep of two tendon types (tibialis anterior, peroneus longus). 80 tibialis anterior and 83 peroneus longus tendons from 51 human cadavers were included. The samples were removed, placed in a radio-cryoprotectant solution, then slowly cooled, sterilized and stored at -80 °C. All groups were subject to 60 s static creep test with 250 N load. Deformation during the loading phase, creep during static loading, and the ratio of these two were evaluated. Deformation at the end of the loading phase and creep consistently exhibited significantly smaller values in the tibialis anterior compared to the peroneus longus type, as well as in electron beam-sterilized grafts as opposed to gamma beam-sterilized ones. Prolonged storage periods (within 0 to 4 months) resulted in a notable increase in these values, particularly in deformation. Based on the experimental data, the tibialis anterior tendon type and sterilization by gamma beam irradiation are better choices for anterior cruciate ligament reconstruction than the peroneus longus and sterilization by electron beam. Increased storage time affects negatively the evaluated mechanical properties.

The sum of the parts: what we can and cannot learn from comorbidity scores in allogeneic transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) requires the comprehensive evaluation of patients across multiple dimensions. Among the factors considered, comorbidities hold great significance in the pretransplant assessment. As many as 40% of alloHCT recipients will have a high burden of comorbidities in contemporary cohorts. To ensure a standardized evaluation, several comorbidity scores have been developed; however, they exhibit variations in properties and performance. This review examines the strengths and weaknesses associated with these comorbidity scores, critically appraising these models and proposing a framework for their application in considering the alloHCT candidate. Furthermore, we introduce the concept that comorbidities may have specific effects depending on the chosen transplantation approach and outline the findings of key studies that consider the impact of individual comorbidities on alloHCT outcomes. We suggest that a personalized transplantation approach should not rely solely on the overall burden of comorbidities but should also take into account the individual comorbidities themselves, along with other patient, disease, and transplantation-related factors.

The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally.

The ideal curative therapy for sickle cell disease (SCD) must be applicable across all ages and include individuals with strokes and preexisting heart, lung, and kidney disease. Myeloablative, matched sibling donor hematopoietic stem cell transplant (HCT) for children with SCD has shown excellent outcomes over the past 3 decades but has been restricted due to the limited availability of a human leukocyte antigen-matched sibling donor (10%-15%) and increased treatment-related death in adults with myeloablative conditioning. To overcome these 2 significant barriers to curative therapy in SCD, related haploidentical HCT has become an active area of research. The use of related haploidentical donors (first- and second-degree relatives) increases the donor pool to at least 90% of those eligible across the life span. Importantly, most adults, even with strokes or significant comorbidities, can tolerate the nonmyeloablative conditioning regimen without treatment-related death. Since 2013, at least 3 related haploidentical HCT strategies have emerged as potential curative therapies for SCD: (1) a nonmyeloablative, T-cell replete, bone marrow transplant with thiotepa and posttransplant cyclophosphamide with a goal of complete donor chimerism; (2) a nonmyeloablative, in vivo T-cell depletion, using peripheral blood stem cells (PBSCs) with a goal of stable mixed donor-recipient chimerism; and (3) a myeloablative, ex vivo T-cell depletion using PBSCs and advanced-technology graft manipulation, with a goal of complete donor chimerism. We review the similarities, differences, outcomes, and gaps in knowledge with these 3 haploidentical HCT approaches for SCD.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

Evaluation of prolonged magnesium infusion after allogeneic hematopoietic cell transplant.

PURPOSE: Calcineurin inhibitor use after allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant magnesium wasting. Utilization of a prolonged magnesium infusion is thought to lead to a lower serum peak concentration and therefore, decreased renal wasting of magnesium. In November 2017, our institution implemented a modification to our inpatient electrolyte replacement protocol for allo-HCT recipients that extended the magnesium infusion rate from 4 g/2 h to 4 g/4 h based on this theoretical advantage. The primary objective of this study was to compare the median magnesium requirements per day of admission between patients who received magnesium 4 g/2 h to patients who received magnesium 4 g/4 h. Secondary objectives included a comparison of the per-patient median serum magnesium concentration during admission, as well as the median incremental difference in serum magnesium concentration after intravenous replacement per patient per admission. METHODS: Allo-HCT recipients who received prolonged infusion magnesium infusions were compared to a historical cohort of allo-HCT patients who received shorter IV magnesium infusions. Admissions were included if the patient had received an allo-HCT within 100 days prior, was admitted to the Transplant and Cellular Therapy Unit at WVU Medicine J.W. Ruby Memorial Hospital, and received at least one magnesium infusion and one dose of cyclosporine or tacrolimus. Admissions were excluded if the patient received oral magnesium, total parenteral nutrition, aminoglycosides, amphotericin, carboplatin, cisplatin, or foscarnet. RESULTS: The pre-implementation group consisted of 81 admissions (n = 64 patients), while the post-implementation group consisted of 90 admissions (n = 60 patients). Median magnesium requirements per day of admission were not different between groups at 1.4 g of magnesium in the pre-implementation group and 1.9 g of magnesium in the post-implementation group (P = 0.25). Median serum magnesium concentrations and median incremental difference in serum magnesium concentration after intravenous replacement were also not different between groups: 1.65 mg/dL vs 1.60 mg/dL (P = 0.65) and 0.30 mg/dL vs 0.28 mg/dL (P = 0.67), respectively. CONCLUSIONS: Prolonged infusion of magnesium in allo-HCT recipients receiving CNI therapy does not result in improvement in magnesium retention.

Recent advances in allogeneic transplantation for acute myeloid leukemia.

PURPOSE OF REVIEW: This review highlights recent advancements in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML). RECENT FINDINGS: Important improvements have been observed throughout the allo-HSCT procedure and patient management. Universal donor availability and reduced risk of graft-versus-host disease (GVHD) have been achieved with the introduction of posttransplant cyclophosphamide for GVHD prophylaxis. It has contributed, together with advances in conditioning regimens, GVHD treatment and supportive care, to a reduced overall toxicity of the procedure. Relapse is now the most frequent cause of transplant failure. With increased knowledge of the biological characterization of AML, better prediction of transplant risks and more profound and standardized minimal residual disease (MRD) monitoring, pharmacological, and immunological strategies to prevent relapse are been developed. SUMMARY: Allo-HSCT remains the standard of care for high-risk AML. Increased access to transplant, reduced toxicity and relapse are improving patient outcomes. Further research is needed to optimize MRD monitoring, refine conditioning regimens, and explore new GVHD management and relapse prevention therapies.

Efficacy of Autologous Hematopoietic Stem Cell Transplantation versus Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation for Follicular Lymphoma: Systematic Review and Meta-Analysis.

BACKGROUND: The effect of autologous hematopoietic stem cell transplantation (auto-HSCT) versus conventional chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the survival of patients with advanced follicular lymphoma (FL) is uncertain. OBJECTIVES: To elucidate this, FL and HSCT were used as keywords to search in PubMed, Embase, Web of Science, and Cochrane Library databases. METHOD: After data extraction and quality evaluation, a total of 13 studies were included, seven of which compared auto-HSCT with conventional chemotherapy and the other six compared allo-HSCT with auto-HSCT to the survival of FL patients. RESULTS: The results showed that auto-HSCT improved overall survival (OS), progression-free survival, and event-free survival of FL patients compared with conventional chemotherapy without auto-HSCT. Compared with allo-HSCT, the patients receiving auto-HSCT had longer OS and lower non-recurrent mortality. CONCLUSIONS: Auto-HSCT can provide a survival advantage for patients with FL compared with conventional chemotherapy and allo-HSCT did not result in a survival benefit.

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.

Bone Marrow Quality Index: A Predictor of Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplantation for Thalassemia.

Bone marrow (BM) continues to be the preferred source of stem cells in allogenic transplantation for nonmalignant disorders. Granulocyte colony-stimulating factor (G-CSF)-primed BM is associated with low rates of acute graft-versus-host disease (aGVHD) and allows reduced collection volumes while ensuring speedy engraftment. However, variability in BM harvest quality is a concern. This study evaluated the utility of a novel indicator, the Bone Marrow Quality Index (BMQI), to predict aGVHD. We analyzed 184 consecutive first matched related donor bone marrow transplants for thalassemia using G-CSF-primed bone marrow over 6 years from March 2017 to April 2023 across 2 centers in India. BMQI was defined as the ratio of the G-CSF-primed BM WBC count to the peripheral blood WBC count within 24 hours of harvest. European Society for Blood and Marrow Transplantation criteria were used to grade aGVHD. The log-rank test was used to assess the impact of BMQI on aGVHD. The chi-square test was used to compare categorical data, and the Wilcoxon rank-sum test was used to compare the numerical data. A Cox proportional hazards model was used to investigate the association of BMQI vis-à-vis other factors on aGVHD. Of the 184 patients studied, 19 had a BMQI <.9, 18 had a BMQI between .9 and 1, and the remaining 147 had a BMQI >1. The rate of aGVHD grade II-IV was 37% in patients with a BMQI <.9 , 22% in those with BMQI .9 to 1, and 12% in those with BMQI >1 (P = .018). Patients with BMQI <.9 had a 3.1-fold greater chance (95% confidence interval [CI], .9 to 10.6) and those with BMQI .9 to 1 had a 2-fold greater chance (95% CI, .5 to 6.6) of developing aGVHD grade II-IV. BMQI was the significant predictor associated with aGVHD hazard (P = .014). BMQI appears to be the most relevant and controllable predictor of aGVHD. It is a novel, informative, and very simple indicator that could influence aGVHD prophylaxis decision making. Our indicator is accurately measurable, inexpensive, precise, and timely; furthermore, it does not involve any sophisticated equipment and thus may be widely applicable. Prior knowledge of poor BM quality may help intensify prophylaxis and monitoring for aGVHD, as well as trigger a review of collection procedures.

Splenic irradiation prior to allogeneic transplant conditioning in myelofibrosis: A pilot experience.

INTRODUCTION: In the era of JAK inhibitors, allogeneic stem cell transplantation (HSCT) remains the only curative treatment for patients with Myelofibrosis (MF). Splenic irradiation (SI) may be used to reduce spleen size and related symptoms. METHODS: We conducted a retrospective analysis on 14 patients with MF who underwent HSCT with SI from any donor source at our center between June 2016 and March 2021. All patients received a conditioning backbone based on treosulfan and fludarabine, with post-transplant cyclophosphamide (PTCy) and sirolimus as graft-versus-host disease (GvHD) prophylaxis. Patients received SI with 10 Gy involved-field radiotherapy in five 2-Gy fractions over the course of a week prior to the beginning of conditioning. RESULTS: At transplant all patients were transfusion-dependent and had splenomegaly (median bipolar diameter by ultrasound: 20.75 cm). Overall, 12 patients had received ruxolitinib prior to transplant. Re-evaluation of spleen dimensions was available for 13 patients: median splenic bipolar diameter after at least 3 months from transplant decreased by a median of 25%. With a median post-transplant follow-up of 25 months, 6 patients remain in CR with full-donor chimerism, 3 patients died due to NRM. Overall, 4 patients relapsed. At last follow-up, nine patients are currently alive and achieved transfusion-independence. CONCLUSIONS: In a small cohort of mostly ruxolitinib pre-treated patients, SI and treosulfan-based conditioning appeared a safe and effective tool to reduce spleen dimensions and ameliorate symptoms. Future prospective studies with adequate sample size are warranted to further investigate the usefulness and safety of this approach in MF.