Search

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons in the brain, brainstem, and spinal cord. It has been proposed that bone marrow (BM)-derived cells might supply motor neurons and other cells with a cellular milieu more conducive to survival in ALS. Direct injection of stem cells in ALS is problematic because of the large expanse of the neuraxis that would need to be injected. We reasoned that transiently increasing the number of circulating hematopoietic stem cells might be a useful therapeutic approach. However, agents stimulating the activation and mobilization of hematopoietic stem cells may have adverse effects such as activation of microglial cells. We conducted a small pilot trial of the collection and reinfusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) in ALS patients and found no adverse effects, paving the way for a properly powered therapeutic trial with an optimized regimen of G-CSF. Muscle Nerve, 2007. [ABSTRACT FROM AUTHOR]

Despite numerous strategies, the cure of multiple myeloma remains a difficult challenge. Recent approaches have involved dose-intensive therapy followed by stem cell transplantation, most often with autologous stem cells (ASCT). Although ASCT is of benefit, it is not considered curative. Between 1988 and 1995, we utilized an aggressive three-drug conditioning regimen followed by ABMT using marrow purged with either 4-hydroperoxycyclophosphamide (4-HC) or mafosphamide (MAF). Twenty-nine of 42 patients who had first received VAD (14 patients) or VAD followed by cyclophosphamide (7 g/m2i.v.) + dexamethasone (40 mg/day p.o. ×4) + GM-CSF (15 patients) met the eligibility criteria needed to undergo bone marrow harvest and ABMT, ie 10% marrow plasma cells and 50% decrease in paraprotein level. Alpha-interferon maintenance therapy was given post ABMT. Median follow-up is 7.5 years (range 5.0–11.25). Six early and two late non-relapse deaths occurred; 15 patients have relapsed. Seven patients remain in continuous CR (five) or PR (two), including three with stage IIIB disease at diagnosis. One patient developed a soft tissue sarcoma 8 years post ASCT. Although this protocol produced excessive toxicity compared with current approaches, the results demonstrate that dose-intensive therapy and ASCT can produce durable remission in this disease. Further development of dose-intensive strategies is warranted. Bone Marrow Transplantation (2000) 26, 621–626. [ABSTRACT FROM AUTHOR]

A 47-year-old male patient developed sepsis and monoarticular arthritis following autologous stem cell transplantation for recurrent Hodgkin’s disease. Blood cultures were positive for Agrobacterium yellow group. The knee pain and swelling responded promptly to the institution of empirical broad-spectrum antibiotics. Recurrent bacteremia developed necessitating Hickman line removal for eventual resolution of the infection. Transplant physicians should be aware of this unusual pathogen and the potential for both persistent line-related sepsis and possible septic arthritis. Bone Marrow Transplantation (2000) 26, 101–104. [ABSTRACT FROM AUTHOR]

Twenty-six patients with low-grade lymphoma (LGL) (n = 18) or chronic lymphocytic leukemia (CLL) (n = 8) received allogeneic BMTs between 1985 and 1998. Median age was 42 years, median interval from diagnosis to transplant 22 months and median number of prior treatments three. Twenty (77%) had stage IV disease; 22 (85%) had never achieved CR. Donor source was HLA matched sibling (n = 19, 73%), matched unrelated (n = 6, 23%) or syngeneic (n = 1). Conditioning therapy included total body irradiation in 23 patients and busulphan in three. Twenty-five received GVHD prophylaxis with cyclosporine A; + methotrexate (n = 19), + methylprednisolone (n = 2) or + T cell depletion of allograft ± methotrexate (n = 4). Sixteen patients are alive, a median of 2.4 years post BMT. Death occurred due to transplant complications (n = 7) or underlying disease (n = 3). Eighteen (12 LGL, six CLL) of 22 evaluable patients (82%) achieved CR post BMT. Cumulative incidence of refractory/recurrent disease was 18% (95% confidence interval (CI) 7–42%). Overall and event-free survivals were 58% (95% CI 35–75%) and 54% (95% CI 32–72%), respectively. Allogeneic BMT for young patients with advanced LGL or CLL is feasible and can result in long-term disease-free survival. Bone Marrow Transplantation (2000) 25, 605–612. [ABSTRACT FROM AUTHOR]

This analysis compares the regimen-related toxicity (RRT) and overall non-relapse mortality (NRM) in Hodgkin’s disease patients conditioned with either CBV (cyclophosphamide, BCNU (carmustine), and VP16–213 (etoposide)) (26 patients) or CBVP (CBV + cisplatin) (68 patients) followed by autologous stem cell transplantation (ASCT). CBVP included a continuous infusion rather than intermittent doses of etoposide, a lower BCNU dose and the addition of cisplatin. RRT and NRM were determined for each regimen and compared; risk factors for each were examined by multivariate analysis. Grade IV (fatal) RRT occurred in five patients (pulmonary in two, cardiac in two, and central nervous system in one). Eighteen patients experienced grade II–III pulmonary RRT, consistent with BCNU damage in 15. Prior nitrosourea exposure was the main risk factor for pulmonary RRT. Grade II mucosal and hepatic RRT occurred less often after CBVP vs CBV (P = 0.031 and 0.0003, respectively). In addition, three other early and eight late non-relapse deaths were seen. Median follow-up of the entire group is 5.1 (range 2.8–10.2) years. The probability of overall NRM was 26% (95% confidence interval (CI) 13–50%) with CBV vs23% (95% CI 12–41%) with CBVP (P = 0.40). The progression-free survival and relapse rates were similar. Although the rates of fatal RRT, pulmonary RRT and overall NRM were similar with CBV or CBVP, CBVP produced less mucosal and liver RRT with a comparable antitumor effect. As many autografted patients are cured, future efforts should include measures to decrease NRM. [ABSTRACT FROM AUTHOR]

Between June 1988 and May 1996, 428 patients underwent allogeneic BMT (288 related donor (RD) and 140 unrelated donor (UD)) at the Vancouver General Hospital. Eight patients (UD six and RD two) developed a post-transplant lymphoproliferative disorder (PTLD). Median age at BMT was 38 years (range 22–51). Five of the six UD allografts were T cell depleted. Cyclosporine ± methotrexate was used for GVHD prophylaxis. All eight patients developed GVHD; in six this was refractory to treatment with corticosteroids. Rabbit antithymocyte globulin (ATG) or an anti-CD5-ricin A chain immunotoxin (Xomazyme) was used as second-line therapy for GVHD. Presentation with PTLD occurred at median day 90.5 (range 34–282) post BMT. Five of the eight patients had a rapidly progres- sive course characterized by fever, lymphadenopathy, lung and liver involvement and died within 3–8 days. PTLD was an incidental finding at post mortem examination in two patients. The remaining patient had localized disease and recovered. Pathological analysis revealed two morphological patterns; diffuse large B cell lymphoma (DLBC lymphoma, five patients) and polymorphous B cell hyperplasia (PBCH, three patients). EBV expression was positive in all eight cases and monoclonality was demonstrated in seven cases. In multivariate analysis, T cell depletion of the allograft (P = 0.0001, relative risk (RR) = 30.5), anti-T cell therapy for GVHD (P = 0.006, RR = 12.7) and acute GVHD grades 3–4 (P = 0.04, RR = 7.7) were the significant factors for development of PTLD. In conclusion, we have identified two forms of PTLD after BMT: one is characterized by disseminated disease with a rapidly progres- sive and often fulminant course and the other by localized, relatively indolent disease. Morphology, EBV positivity and clonality do not appear to correlate with the clinical course. The major risk factors for development of PTLD after BMT are ex vivo T cell depletion of the allograft and... [ABSTRACT FROM AUTHOR]

While allogeneic stem cell transplantation (SCT) is curative for a significant number of patients with AML, relapse of disease within the bone marrow and/or extramedullary (EM) sites following high-dose therapy continues to limit the success of this treatment. Between October 1985 and December 1996, 81 adults underwent allogeneic SCT for de novo AML at our centre. Forty-two patients remain alive and free of leukaemia with a median follow-up of 50 months. The 5-year actuarial event-free survivals (EFS) for all patients and for those undergoing SCT in CR1 or with advanced disease were 46% (95% confidence interval (CI) 34–58%), 63% (CI 46–76%), and 19% (CI 7–36%), respectively. Twenty-two patients relapsed at a median of 8 (range 1.6–54.5) months with the actuarial risk of relapse for all, CR1 and advanced disease patients being 38%, (CI 27–52%), 23% (CI 13–40%) and 68% (CI 46–88%), respectively. Ten patients relapsed at EM sites; six of these (27% of relapses) had an isolated EM relapse at a median of 31 (range 8.5–54) months. Three of the patients with isolated EM relapse survived 24 months following relapse and two patients remain disease-free at 29+ and 33+ months. BuCy conditioning followed by allogeneic SCT in AML results in satisfactory EFS although there is a significant risk of late isolated EM relapse. [ABSTRACT FROM AUTHOR]

The role of ICU support in BMT patients is controversial. In an era of constrained resources, the use of prognostic factors predicting outcome may be helpful in identifying patients who are most likely (or unlikely) to benefit from this intervention. We attempted to define the survival of patients admitted to ICU following autologous or allogeneic BMT and to identify those factors important in determining patient outcome. A retrospective study of all adult BMT recipients admitted to intensive care over a 6 year study period was performed to determine overall and prognostic indicators of poor outcome. Pre-treatment, pre-ICU admission and ICU admission data were analyzed to identify factors predicting long-term survival. 116 patients were admitted to ICU on 135 separate occasions with the primary reasons for admission being respiratory failure (66%), sepsis associated with hypotension (10%), and cardiorespiratory failure (8%). No pre-ICU characteristics were predictive of survival. Univariate analysis identified the number of support measures required, the need for ventilation or hemodynamic support, the APACHE II score, the year of ICU admission and the serum bilirubin as significant predictors of post-discharge survival. On multivariate analysis the year of ICU admission, the need for hemodynamic support and the serum bilirubin remained significant. The APACHE II score significantly underestimated survival in the 46% of patients with scores less than 35, and could only be used to predict 100% mortality when it exceeded 45. Twenty-three percent of all BMT patients admitted to the ICU and 17% of ventilated patients survived to hospital discharge. Of the 27 patients surviving to leave hospital, 16 remain alive with a median follow-up of 4.2 years and a mean Karnofsky performance status of 90. Although mortality in BMT recipients admitted to ICU is high our results indicate that intensive care support can be lifesaving and that the outcome in patients requiring... [ABSTRACT FROM AUTHOR]

Introduction: Anti-thymocyte globulin (ATG) has been demonstrated to reduce the incidence of graft-versus-host disease (GVHD); however, it remains controversial whether these gains are offset by an increase in relapse., Methods: We conducted a retrospective historical control study consisting patients (n=210) who underwent myeloablative allogeneic hematopoietic stem-cell transplantation (HSCT) from 2014 to 2020., Results: The incidence of acute GVHD was lower in the ATG group (51.4%) than the non-ATG group (control) (70.0%, p=0.010). The incidence of chronic GVHD was also lower in the ATG group at 1-year (36.4% vs. 62.9%, p <0.001) and 2-year (40.0% vs. 65.7%, p <0.001) post-HSCT. The mortality due to GVHD was higher in the control (18.5%) than the ATG group (4.3%; p= 0.024). The severe GVHD-relapse-free survival was higher in the ATG group (36.4%) than the control (12.9%; p <0.001). Nevertheless, the 2-year overall survival was similar., Conclusion: Our results confirm the effectiveness of ATG in prevention of GVHD in the real-world setting and enhanced GVHD-free survival. An important result is the equalization of overall survival between the ATG and control groups at 1- and 2-year post-HSCT and implies that earlier GVHD-associated mortality may be offset by later relapse mortality producing similar overall survival over time., (S. Karger AG, Basel.)

Background: Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure., Objective: We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC., Study Design: A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure., Results: Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3-99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3-12.3, P < 0.01), primary graft failure (OR 36.3, 5.4-210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7-121.1, P < 0.01)., Conclusions: Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2-3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased., Competing Interests: Declaration of Competing Interest The following authors have financial disclosures as outlined in the following: David Sanford, Membership on an entity's Board of Directors or advisory committees (Abbvie, Astellas); Kevin Song, honoraria (Janssen, Sanofi, BMS, Forus, Amgen, GSK, Gilead, Novartis); Shanee Chung, Consultancy & honoraria (Takeda), Honoraria (Astella Pharma, Novartis, Paladin, Pfizer); Ryan Stubbins, Honoraria (AbbVie, Pfizer, Jazz, Takeda), Advisory board (AbbVie), Research funding (Jazz); Heather Sutherland, Honoraria (Amgen, Forus, BMS); Kevin Hay, research funding (Janssen), Honoraria (BMS, Kite/Gilead, Novartis). The remaining authors have no competing interests or financial disclosures., (Copyright © 2024 International Society for Cell & Gene Therapy. All rights reserved.)

The Canadian Society for Immunology (CSI) established a formal Equity, Diversity, and Inclusion (EDI) Committee with the goal of providing EDI advocacy and leadership within the CSI, as well as in the broader scientific community. A first task of this committee was to review the publicly available historical data on gender representation within the CSI's membership, leadership, award recipients, and conference chairs/presenters as a step in establishing a baseline reference point and monitoring the trajectory of future success in achieving true inclusion. We found that, except for overall membership and a specific subset of awards, all categories showed a historical bias toward men, particularly prior to 2010. Bias persists in various categories, evident even in recent years. However, we note an encouraging trend toward greater gender parity, particularly in the roles of President, symposium presenters, and workshop chairs, especially from 2017 onward. We present these findings as well as our recommendations to enhance inclusivity. These include a more comprehensive collection and secure storage of self-identification data, emphasis on EDI as an essential component of all annual meeting activities, and innovative measures of outreach, collaboration, and leadership with the aim of making the CSI a model for improving EDI in other professional research societies., (Copyright © 2024 by The American Association of Immunologists, Inc.)