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In this study of unrelated-donor transplantation for hematologic cancers, survival was similar with bone marrow and peripheral-blood stem-cell grafts. However, graft failure was more common with the former, and chronic graft-versus-host disease with the latter. In the early days of allogeneic hematopoietic stem-cell transplantation, the only graft source available was bone marrow harvested from the pelvis of a donor under anesthesia. When studies showed that an increased dose of bone marrow cells correlated with more robust hematopoietic engraftment and lower mortality from infectious complications, transplantation centers began to use filgrastim-stimulated peripheral blood, which has a much higher content of blood progenitor cells than bone marrow, although there was concern that the higher T-cell content might increase the risk of graft-versus-host disease (GVHD). 1 – 5 Several large, randomized trials of transplantation between HLA-identical siblings showed that peripheral-blood . . .

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18–83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8–20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24–48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55–2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc.

Purpose The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be lowered after core decompression. In earlier non-fracture ON stages, implantation of autologous bone marrow aspirate concentrate (BMAC) improved the effect of core decompression. The purpose was to evaluate the effect of BMAC in addition to core decompression in stage 3 ONFH. Methods A double blind RCT was conducted comparing two groups: core decompression plus saline injection or core decompression plus BMAC implantation. Both patients and assessors were blinded to the treatment assignments. Evaluations were done at baseline, three, six, 12, and 24 months, including pain (VAS), WOMAC, side-effects, radiological evolution including ARCO subclassifications, together with possible THR requirement. The primary endpoint was the need for THR. The second endpoints included the clinical symptoms such as pain and functional ability and the progression of the ON lesions as well as the appearance of osteoarthritis features (ARCO stage 4). Both groups included 23 hips (19 patients). Results No differences were found between the groups for THR requirements, clinical tests, and radiological evolution. In both groups, 15/23 hips needed THR. The radiological evolution of the ONFH lesions in term of location, extension, surface collapse, and dome depression was moderate in both groups and was not correlated with the need of THR. Conclusions Implantation of BMAC after core decompression did not produce any improvement of the evolution of ONFH stage 3. Level of evidence I.

To promote the regeneration of myocardial cells after myocardial infarction, intracoronary infusion of bone marrow cells, which contain stem cells and progenitor cells, has been investigated. In this study of patients with acute anterior myocardial infarction, infusion of bone marrow cells had no effect on left ventricular function or infarct size 6 months after the infarction. In this study of patients with acute anterior myocardial infarction, infusion of bone marrow cells had no effect on left ventricular function or infarct size 6 months after the infarction. Contrary to previous belief, there is evidence of regeneration of the myocardium throughout life, and the rate of this regeneration is increased after large myocardial infarctions. 1 However, regeneration seems to be limited to the viable myocardium and its border zone, 1 and the net loss of cardiomyocytes during myocardial infarction is a key factor in the resulting remodeling and in the impairment of cardiac-pump function. 2 , 3 The bone marrow harbors stem cells and progenitor cells that may be capable of solid-organ repair. 4 In experimental models of myocardial infarction, intramyocardial or intravenous injections of cells derived from bone marrow (BMC) have resulted . . .

Background Haematological cancer affects more than 1.3 million people around the world annually and accounted for almost 800,000 deaths globally in 2020. The number of patients with these cancers undergoing bone marrow transplant is increasing. Of note, this intensive treatment is associated with complex and multifactorial side effects, often impacting nutritional status, physical functioning and overall health-related quality of life. The primary aim of this study is to investigate the effectiveness of an eight-week multidisciplinary rehabilitation intervention compared with usual care on the physical function domain of the European Organisation for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30 version 3) in patients with haematological cancer following bone marrow transplant. Methods This is a multisite, pragmatic two-arm parallel-group, randomised controlled trial (RCT) with stratified randomisation, powered for superiority, recruiting 170 participants at 30 days following either allogeneic or autologous bone marrow transplant (ACTRN12622001071718). Recruitment sites include three Australian university affiliated teaching hospitals. Participants are eligible if aged ≥ 18 years, treated for haematological cancer with allogeneic or autologous bone marrow transplant and can walk independently. The intervention group will receive eight weeks of twice weekly telehealth-based exercise classes, an initial and follow up dietetics consult, post exercise protein supplements, and a home-based physical activity program, all with embedded behaviour change strategies. The primary outcome is patient reported physical function measured using the EORTC QLQ-C30 version 3. Secondary outcomes include other domains of the EORTC QLQ-C30, fatigue, physical function, physical activity levels, frailty, body composition, sarcopenia and nutrition assessment. We will also undertake a health economic analysis alongside the trial and a process evaluation exploring intervention fidelity, causal mechanisms as well as contextual influences through qualitative enquiry. Discussion The REBOOT trial will add RCT-evidence from a rigorously conducted, statistically powered multi-site trial to existing limited knowledge on the effects of multi-disciplinary rehabilitation for people with haematological cancer. If effectiveness is supported, then implementation of rehabilitation into care pathways for people having bone marrow transplant can be considered. Trial registration ACTRN12622001071718 prospectively registered 03/08/2022, last updated 08/03/2024.

The alarming disability burden and a high prevalence rate of stroke in India has encouraged the researchers to develop regenerative therapies to reduce clinical deficits. This study evaluates safety, feasibility and efficacy of autologous mononuclear and mesenchymal cell transplantation in stroke patients evaluated on clinical scores and functional imaging (fMRI and DTI). Forty (n=40) stroke patients were recruited with the inclusion criteria as: 3 months to 2 years of index event, power of hand muscles of at least 2; Brunnstrom stage: 2–5; conscious and comprehendible. Fugl Meyer (FM), modified Barthel Index (mBI), Medical Research Council (MRC) grade for strength, Ashworth tone scale and functional imaging was used for assessments at baseline, 8 weeks and 24 weeks. 50–60 million cells in 250ml saline were infused intravenously over 2–3h. The safety test profile was normal with no mortality or cell related adverse reactions in stem cell patients. Among outcome parameters, only modified Barthel Index (mBI) showed statistical significant improvement (p<0.05) in the stem cell group. An increased number of cluster activation in Brodmann areas BA 4, BA 6 was observed post stem cell infusion indicating neural plasticity. Autologous intravenous stem cell therapy is safe and feasible. Stem cells act as “scaffolds” for neural transplantation and may aid in repair mechanisms in stroke.

Background Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. Methods A total of 345 subjects were prospectively recruited and randomly selected as training group ( n  = 173) and validation group ( n  = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). Results A total of 342 patients (99.1 %) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8–28 days) and 18 days (range, 6–330 days), respectively. The cumulative incidence of primary GF was 6.4 ± 1.3 % and included GR (0.9 ± 0.5 %) and PGF (5.5 ± 1.2 %). Of the 345 cases tested, 39 (11.3 %) were DSA positive. Multivariate models showed that DSAs (MFI ≥ 10,000) were correlated to primary GR ( P  < 0.001) and that DSAs (MFI ≥ 2000) were strongly associated with primary PGF ( P  = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 ( n  = 316), group B included cases with a 2000 ≤ MFI < 10,000 ( n  = 19), and group C included cases with a MFI ≥10,000 ( n  = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60 %, for groups A, B, and C, respectively, P  < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3 %, for groups A, B, and C, respectively, P  = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4 %, for groups A, B, and C, respectively, P  = 0.015). The primary GF was independently associated with a higher incidence of TRM ( P  < 0.001), inferior disease-free survival ( P  < 0.001), and OS ( P  < 0.001). Conclusions The findings confirmed the effect of DSAs on primary GF, including GR and PGF, and survival. Our results suggest incorporating DSAs in the algorithm for haploidentical donor selection.

Background Hematopoietic stem cell transplantation (HSCT) is a common therapy for many hematologic malignancies. While advances in transplant practice have improved cancer-specific outcomes, multiple and debilitating long term physical and psychologic effects remain. Patients undergoing allogeneic bone marrow transplantation (allo-BMT) are often critically ill at initial diagnosis and with necessary sequential treatments become increasingly frail and deconditioned. Despite modern treatment regimens and support, cardiovascular disease remains a leading cause of non-relapse mortality among allo-BMT survivors. Well-established multi-disciplinary care models such as cardiac rehabilitation offer holistic care including exercise training, nursing support, physical/occupational therapy, psychosocial support and nutritional education. HSCT patients may be excluded from conventional outpatient physical rehabilitation programs due to prolonged pancytopenia and frequent hospital admissions. In Canada, dedicated cancer-specific rehabilitation programs are available only at major tertiary academic centers. Methods The primary aim of this study will evaluate the feasibility and acceptability of a multimodal care navigation (nursing, exercise, nutrition) intervention with content delivery facilitated by a supportive care web-based ‘app’ extending from diagnosis to 1 year in the allogeneic bone marrow transplant population. Adult patients scheduled for allo-BMT will receive support from exercise specialist, nursing support and dietician expertise alongside a supportive care ‘app’ with additional in-person or virtual cardiac rehabilitation support. Discussion To our knowledge, no research team is taking such a holistic, multidisciplinary approach to address the debilitating physiologic and psychological consequences of allo-BMT. We expect the findings to inform the optimal timing and patient preferences to develop studies examining risk-specific, individualized interventions (including exercise, pharmacotherapy, combination treatments) to reduce or prevent symptoms and dysfunction. We expect this innovative program to identify ways to benefit innumerable patients with hematologic and other malignancies. Ultimately, we hope to transform supportive care in hematopoietic stem cell transplantation. Trial Registration Clinicaltrials.gov ID: NCT05579678.

The infusion of bone marrow–derived progenitor cells into the infarct-related coronary artery after an acute myocardial infarction was associated with an absolute increase in the ejection fraction of 5.5%. Determining whether this modest improvement in ventricular function will translate into a long-term clinical benefit will require larger trials with longer follow-up. The infusion of bone marrow–derived progenitor cells into the infarct-related coronary artery after an acute myocardial infarction was associated with an absolute increase in the ejection fraction of 5.5%. Prompt reperfusion of the infarct-related coronary artery has considerably improved the clinical outcome in patients with acute myocardial infarction. 1 Although contemporary reperfusion strategies using stent implantation and aggressive inhibition of platelet aggregation have been shown to increase myocardial salvage, 2 improvements in global left ventricular function are rather modest, despite the use of optimal reperfusion therapy. 3 , 4 Heart failure that develops after infarction remains a major cause of morbidity and mortality. 5 , 6 Experimental studies suggested that intravascular or intramyocardial administration of progenitor cells derived from bone marrow (BMC) or blood may contribute to functional regeneration of infarcted myocardium and enhance neovascularization . . .

The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM—157; PB—157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II–IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.