Autologous Hematopoietic Stem Cell Transplantation for Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge. OBJECTIVE: To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT). METHODS: This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications. RESULTS: Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24-46 years), with a median delay of 46 months (range 21-135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses. CONCLUSIONS: AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.

Does Lymphocyte Count Impact Dosing of Anti-Thymocyte Globulin in Unrelated Donor Stem Cell Transplantation?

Anti-thymocyte globulin (ATG) is used to reduce the incidence and severity of graft-versus-host disease (GVHD) with hematopoietic cell transplantation, yet optimum dosing has yet to be determined. We have previously demonstrated that 2.5 mg/kg ATG in conditioning can reduce the incidence of GVHD in unrelated donor transplants. Recent literature has suggested that ATG dosing based on absolute lymphocyte count (ALC) could lead to more optimum exposure of the drug. We sought to determine if ALC at the time of transplant could impact clinical outcomes. We conducted a retrospective single-center study analyzing all consecutive patients at The Ottawa Hospital who received a matched unrelated donor stem cell transplant with ATG between 2009 and 2014. Patients received rabbit ATG (thymoglobulin) at 0.5 mg/kg on day -2 and 2.0 mg/kg on day -1. Univariate and multivariate analyses were used to determine if any patient- or transplant-related factors, including weight, ALC, and total ATG dose given, impacted GVHD, relapse, or mortality. In total, 111 patients met inclusion, with a median age of 50 years (range, 19 to 70). The most common diagnoses were acute myelogenous leukemia (43%), Myelodysplasia/myeloproliferative neoplasms (13%), and lymphoma (12%). The median weight at time of conditioning was 80.3 kg (range, 45 to 216). The median ALC on the first day of ATG administration was 0.1 × 109/L (range, 0 to 190). The median total dose of ATG received was 201 mg (range, 112 to 540 mg). The incidence of acute and chronic GVHD was 35.1% and 21.6%, respectively. In the multivariate model, the actual dose of ATG given to patients was not associated with GVHD (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.99 to 1.25; P = .07), relapse (HR, 1.13; 95% CI, 0.98 to 1.30; P = .1), or mortality (HR, 1.09; 95% CI, 0.92 to 1.28; P = .32). Similarly, the pretransplant ALC was not associated with GVHD (HR, 1; P = .82), relapse (HR, 1; P = .90), or mortality (HR, 1; P = .39). If patients had received ALC-based dosing according to previously published work (Admiraal et al., Lancet Haematol 2017), the mean total dose of ATG received would have been 1205 mg, more than 5 times the mean dose that was actually given based on weight. With GVHD outcomes being similar to that published by Admiraal et al. and ALC not independently associated with outcomes in our study, further studies are still needed to compare standard weight-based dosing to ALC-based dosing of ATG in matched unrelated donor stem cell transplant.

Effect of Donor Age and Donor Relatedness on Time to Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia.

Relapse after allogeneic hematopoietic cell transplantation (HCT) for acute leukemia can be reduced when pursued early after first complete remission. The impact of donor age and donor relatedness on the time from diagnosis to transplant in patients with acute leukemia was examined to clarify the design of future prospective studies that can address optimal donor choice. Files of 100 consecutive patients undergoing transplantation for leukemia were reviewed. Recipients of related donors (RDs) and unrelated donors (UDs) were not significantly different in terms of recipient gender, age, underlying diagnosis, disease risk index, graft source, or donor HLA match. UDs were significantly younger than RDs (median age, 29 versus 51, P < .001). Multivariate linear regression revealed that when controlling for age of donor and recipient, the time from diagnosis to transplant was 35% longer with UDs compared with RDs (P = .018). No significant correlation was observed between donor and recipient age on length of time to transplant (P = .134 and P = .850, respectively), when controlling for other variables. The steps in UD procurement that contribute most to the longer time to transplant relate to activating the donor workup and scheduling the donor workup before cell collection. Understanding sources of delay in the transplant process will help transplant centers and UD registries reduce the time to transplant for patients with acute leukemia and will provide necessary insight for the design of prospective controlled studies that can address optimal donor choice.

Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHCT recipients have historically had low-dose Thymoglobulin (total dose, 2.5 mg/kg; Genzyme-Sanofi, Cambridge, MA) added to our standard MRD GVHD prophylaxis regimen. In this retrospective cohort study we assessed post-HCT the effectiveness of our uniquely low-dose ATG strategy by comparing ATG exposed (MUD) and unexposed (MRD) alloHCT recipients for GVHD and other clinical HCT outcomes. This retrospective single-center study included all HCT patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. MUD patients received rabbit ATG (Thymoglobulin) at a total dose of 2.5 mg/kg given over 2 days (.5 mg/kg on day -2; 2.0 mg/kg on day -1 before stem cell infusion) in addition to standard GVHD prophylaxis. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days, respectively. Secondary outcomes included disease relapse and survival. There were 110 and 77 patients in the ATG exposed (MUD) and unexposed (MRD) cohorts, respectively. At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen, or intensity between cohorts. A higher proportion of 7/8 mismatched donor transplants (13% versus 3%, P = .02) and a higher median CD34+ dose (7.9 versus 4.9 × 108 cells; P < .01) was observed in the ATG exposed cohort. No differences were noted in platelet engraftment. ATG exposed patients had significantly shorter time to neutrophil engraftment than the unexposed cohort (16 versus 19 days, respectively; P < .01). ATG exposed patients had significantly lower rates of GVHD than ATG unexposed patients (57% versus 79%; P = .01), with differences predominantly in rates of chronic GVHD (18% versus 44%, P < .01). At median follow-up of 28 (range, 3 to 69) and 25 (range, 2 to 73) months for survivors in ATG exposed and unexposed cohorts, respectively, no significant differences in overall survival (median overall survival not met for either cohort), relapse incidence (26% versus 29%, P = .73), or relapse-free survival (RFS) (not met in ATG exposed and 26 months in ATG unexposed, P = .22) were observed between groups. The ATG exposed cohort had significantly higher GVHD-free RFS (GRFS) with a 2-year GRFS of 23% versus 3% (P = .003). There were no significant differences between cohorts in proportion of patientswith post-HCT infectious episodes or intensive care unit admissions. Here we report significantly lower rates of chronic GVHD and significant improvement in GRFS in an ATG exposed MUD alloHCT cohort compared with an ATG unexposed MRD cohort. These findings were observed without differences in relapse, survival, infectious complications, or intensive care unit admissions. Our findings highlight the association of unconventionally low-dose ATG with improved GVHD outcomes and suggest a need for prospective study of ATG use in lower doses.

Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial.

BACKGROUND: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis. METHODS: We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930. FINDINGS: Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score. INTERPRETATION: We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs. Furthermore, many of the patients had substantial recovery of neurological function despite their disease's aggressive nature. FUNDING: Multiple Sclerosis Scientific Research Foundation.

Balancing give and take between patients and their spousal caregivers in hematopoietic stem cell transplantation.

OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) is a demanding treatment. Spouses of HSCT patients assume caregiving responsibilities that can induce feelings of burden and disrupt relationship equity. On the basis of equity theory, we propose a conceptual framework examining the individual and dyadic experience of HSCT patients and their caregivers. The model includes feelings of inequity, patient self-perceived burden, caregiver burden, and distress. METHODS: The HSCT patients and their spousal caregivers were recruited prior to HSCT between March 2011 and September 2012. Each member of the dyad self-administered a questionnaire package. RESULTS: Seventy-two dyads were included in the path analyses. Our model demonstrated an inadequate statistical fit; however, with one modification, an adequate to good fit was obtained: χ2 (df) = 6.01(5), normed χ2  = 1.20, standardized root mean square residual = 0.048, comparative fit index = 0.99, Tucker-Lewis index = 0.96, and root-mean-square error of approximation = 0.05 (90% CI, 0.00-0.18). As hypothesized, pre-HSCT caregiver burden mediates the relationship between caregiver underbenefit and caregiver distress. However, patient self-perceived burden was not associated with patient distress; rather, patient perception of overbenefit was related to patient distress. In our modified model, the results demonstrate that patient overbenefit influenced caregiver burden; however, there was not a reciprocal influence, because caregiver variables did not affect patient variables. CONCLUSIONS: Our proposed theoretical framework describes patients' and caregivers' individual experience of distress before HSCT but does not as clearly encompass the dyadic experience. Addressing perceived imbalances and providing psycho-education on role changes within HSCT dyads before transplantation may be a useful prehabilitation strategy for preventing distress.

Improved Prediction of CD34+ Cell Yield before Peripheral Blood Hematopoietic Progenitor Cell Collection Using a Modified Target Value-Tailored Approach.

The most commonly used stem cell source for both autologous and allogeneic transplantation is mobilized peripheral blood hematopoietic progenitor cells collected by apheresis. In the 1990s, an Italian group used the correlation between the preapheresis peripheral blood CD34+ cell count and the final number of CD34+ cells collected to devise a formula for "target value-tailored" (TVT) apheresis. Using local patient data, the Canadian Blood Services Stem Cell Laboratory created a similar model to determine the blood volume to process during apheresis collection. The objectives of this study were to determine the correlation between the number of CD34+ cells predicted by the TVT formula and the actual number of CD34+ cells collected and to determine whether the TVT formula remains predictive when applied to an external data set. All apheresis collections performed at the Ottawa Hospital between January 1, 2003 and October 2, 2013 were reviewed. The primary outcome was the correlation between the number of CD34+ cells predicted by the TVT formula and the actual number of CD34+ cells collected on day 1 of apheresis. For the external data set, all autologous collections performed at the London Health Sciences Centre between December 1, 2008 and December 1, 2013 were reviewed. The external data set was divided into test and validation sets to determine whether a model could be created to predict the final number of CD34+ cells collected on day 1 based on the preapheresis CD34+ count. A total of 1252 collections were included in the analysis. The Ottawa data set included 1012 collections, 836 of which were autologous and 176 of which were from donors. Of the autologous collections in Ottawa, 764 (92.5%) were first collections. In 759 (91%) collections, chemotherapy plus granulocyte colony-stimulating factor (G-CSF) was used as the mobilization regimen. In 747 collections (89%), only 1 collection day was required to achieve the desired number of CD34+ cells. The TVT estimate was highly predictive of the number of CD34+ cells × 10(6)/kg actually collected on apheresis day 1 (r = .90, P < .0001). The London data set included 240 autologous collections. All mobilizations were with G-CSF alone. For the test set, the precollection CD34+ count was highly predictive of the number of CD34+ cells × 10(6)/kg collected on day 1 of apheresis. Applying this model to the validation set, the correlation between the predicted and final and day 1 CD34+ cells × 10(6)/kg count was .9186 (P < .0001). Using a modified TVT approach, the preapheresis CD34+ count can be used to accurately predict the number of CD34+ cells × 10(6)/kg collected on day 1. This approach can be applied at other centers and for different diseases and mobilization regimens. This method can be used to individualize the blood volume processed and, thus, optimize resource utilization.

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

Impact of platelet transfusion on toxicity and mortality after hematopoietic progenitor cell transplantation.

BACKGROUND: Thrombocytopenia occurs commonly after hematopoietic progenitor cell transplantation (HPCT) and is associated with potential morbidity and mortality. Few studies have examined the impact of platelet (PLT) transfusion on clinical outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain uncertain. STUDY DESIGN AND METHODS: A retrospective single-center cohort study was conducted on 522 patients undergoing HPCT between January 2002 and December 2007. Associations between PLT transfusion events and clinical characteristics with transplant-related outcomes were assessed using univariate and multivariate analysis. RESULTS: Mean number of PLT transfusion events before Day +60 posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and multivariate analysis confirmed that the number of PLT transfusion events was associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant length of hospital stay (p < 0.01), need for intensive care unit admission (p < 0.01), and number of organs affected by severe toxicity (p < 0.01). CONCLUSION: HPCT-related toxicity and mortality are associated with increased PLT transfusion events. Alternative strategies to reduce PLT transfusions after HPCT may warrant future study.

Is cytomegalovirus testing of blood products still needed for hematopoietic stem cell transplant recipients in the era of universal leukoreduction?

Hematopoietic stem cell transplantation (HSCT) recipients are a high-risk, immunocompromised group of patients who receive frequent transfusions after transplantation. Transfusion of cytomegalovirus (CMV)-negative blood products has long been the standard of care to prevent transfusion-transmitted CMV in this patient population. Leukoreduction of blood products before transfusion has been shown to significantly reduce the risk of transfusion-transmitted CMV. In the era of universal leukoreduction in Canada, the need for CMV testing of blood products remains unclear. We sought to identify whether there is a difference in transfusion-transmitted CMV viremia in patients receiving only leukoreduced versus CMV-negative and leukoreduced blood products in HSCT recipients. Patients who were CMV negative and received an allogeneic HSCT from a CMV-negative donor between October 1, 1999 and June 30, 2012 were included in the analysis. Transfusion data were collected from The Ottawa Hospital Blood Bank and Canadian Blood Services. CMV viremia was defined as PCR positivity. One hundred sixty-six patients were identified who met the inclusion criteria. Of these, 89 patients received an HSCT before January 2007, during the time when patients received leukoreduced and CMV-negative blood products. Seventy-seven patients received an HSCT after this time, receiving only leukoreduced blood products. The 2 groups did not differ in terms of age, gender, diagnosis, graft type, graft source, conditioning regimen, or ABO compatibility (P > .05). CMV viremia was detected in 3 patients who received CMV-negative leukoreduced blood products (3.37%) and in 1 patient who received only leukoreduced blood products (1.30%, P = .6244). Of the patients who developed CMV viremia, 2 developed suspected CMV disease. Both of these patients were transfused with CMV-negative blood products. Secondary outcomes, including total length of stay in hospital, admission to the intensive care unit, acute and chronic graft versus host disease, and 100-day nonrelapse mortality, did not differ between the groups. In the era of universal leukoreduction of blood products, this study demonstrates that testing for CMV-negative blood products is not needed for HSCT recipients.

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ~48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (~50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.

Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance. METHODS: Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection, and cryopreserved. Immunoablation using busulfan, cyclophosphamide, and rabbit antithymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic, and clinical evidence of rejection while off immunosuppression at 2 y post-aHSCT. RESULTS: Two of the 5 patients achieved operational tolerance with no clinical or histologic evidence of PSC progression or allorejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now >3 y after aHSCT. A fourth patient was weaned off immunosuppression but died 212 d after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T-cell clones, loss of autoantibodies, and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors. CONCLUSIONS: Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed render this specific protocol unsuitable for clinical adoption.

Does Up-front Autologous Stem-Cell Transplantation at First Relapse Improve Outcome in Transplant-Eligible Follicular Lymphoma Patients Whose Disease Relapses Within 24 Months?

BACKGROUND: In Canadian adults, follicular lymphoma (FL) is the most common subtype of non-Hodgkin lymphomas. Approximately 20% of patients with FL experience progression of disease within 2 years of first-line chemoimmunotherapy. Those patients have an expected overall survival of less than 5 years. The optimal second-line treatment for these high-risk patients is unclear. PATIENTS AND METHODS: We analyzed data from the Blood and Bone Marrow Transplantation Center at Ottawa Hospital to determine whether autologous stem-cell transplantation as up-front therapy for first relapse can improve outcomes in this high-risk FL subgroup. We identified 17 patients who underwent up-front autologous stem-cell transplantation between February 2012 and February 2019. RESULTS: The disease of all patients had relapsed within 24 months after receipt of their first rituximab-based chemotherapy. Overall survival at 2 and 5 years was 86.2% (95% confidence interval [CI], 55-96) and 71.8% (95% CI, 31-91), respectively. The progression-free survival at 2 and 5 years was 62.6% (95% CI, 35-81) and 53.6% (95% CI, 25-75), respectively. CONCLUSION: Overall survival is improved when receiving autologous hematopoietic stem-cell transplantation as up-front therapy at first relapse in transplant-eligible FL whose disease relapses within 24 months of first-line therapy. Data from our single center look promising, but the data need to be replicated with a larger sample size.

Increased graft content of vascular progenitor cells is associated with reduced toxicity following autologous hematopoietic transplantation.

OBJECTIVE: Endothelial-like vascular progenitor cells (VPCs) can be collected in peripheral blood stem cell (PBSC) products that are used in hematopoietic stem cell transplantation (HSCT). The association between VPCs in PBSC products and transplant-related toxicity caused by high-dose chemo/radiotherapy was assessed to identify potential mediators of vascular repair. MATERIALS AND METHODS: PBSC grafts in 29 patients (mean age: 48 years; range, 20-67 years) undergoing autologous HSCT were analyzed using a cell culture assay for VPC cluster formation in fibronectin-coated dishes in serum-rich angiogenic conditions. Transplant toxicity was estimated using total length of hospital stay (LOS) following HSCT and the Seattle criteria for transplant-related organ toxicity for 8 organ systems (grade 0-4). RESULTS: LOS following graft reinfusion was lower (14.7 vs 20.0 days, p = 0.002) and the mean number of organs with any toxicity (1.0 vs 2.4, p = 0.016) or with toxicity grade > or = 2 was reduced (0.2 vs 1.6 organs, p = 0.007) in patients with high graft VPC content (n = 10, >2.0 x 10(3) VPCs/kg) compared with reduced VPC content (n = 19, < or = 2.0 x 10(3) VPCs/kg). An association between graft CD34(+) levels and LOS or organ toxicity was not observed. In addition, graft VPC levels were independent of graft CD34 counts, peripheral blood monocytes and hemoglobin levels, age, and disease (p = NS). CONCLUSION: PBSC products enriched for VPCs are associated with reduced toxicity following HSCT. Identifying specific factors that contribute to high graft VPC levels is needed.

Are We Choosing Wisely With Autologous Hematopoietic Cell Transplantation Screening? The Utility of Pulmonary Function Testing Prior to Autologous Hematopoietic Cell Transplantation.

INTRODUCTION: Despite the risk of morbidity and mortality associated with autologous hematopoietic cell transplantation (ASCT), there are no clear guidelines as to how to screen for these risks. This study sought to determine the utility of pulmonary function tests (PFTs) prior to ASCT on predicting posttransplant clinical outcomes. PATIENTS AND METHODS: Patients undergoing ASCT between 2010 and 2012 at the Ottawa Hospital (n = 172) were reviewed. PFT results prior to ASCT were retrieved. The primary outcomes were incidence of intensive care unit (ICU) admission, Seattle Criteria for pulmonary toxicities, and transplant-related mortality (TRM). RESULTS: PFTs were performed for 91 (53%) patients prior to ASCT. There were more smokers in the PFT cohort than the non-PFT cohort (41.8% vs. 19.8%, respectively; P < .0001). Pulmonary toxicity as measured by the Seattle Criteria did not correlate with PFT results (normal vs. abnormal, 8.1% and 6.1%, respectively; P = 1.00). There were no differences in incidence of ICU admission by PFT result (normal vs. abnormal, 2.7% vs. 8.2%, respectively; P = .61) and no difference in TRM by PFT result (normal vs. abnormal, 0% vs. 2.0%, respectively; P = 1.00). CONCLUSION: Despite testing patients deemed higher risk for pulmonary toxicity, abnormal PFTs did not predict for an increased risk of pulmonary toxicity, ICU admission, or TRM at our center.

Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma.

Patients with coexisting medical problems may suffer increased toxicity and reduced quality of life after autologous hematopoietic stem cell transplantation (HSCT). The benefit of high-dose therapy for some patients with multiple myeloma (MM) is debatable. Decision tools that aid in identifying those patients with MM most suited for autologous HSCT may avoid the risk of excess toxicity. An objective assessment of comorbidities was performed in 126 patients with MM undergoing autologous HSCT using the Charlson comorbidity index (CCI), the hematopoietic cell transplantation comorbidity index (HCT-CI), and a modified pretransplantation assessment of mortality (mPAM) to determine the strength of association with increased transplantation-related toxicity and increased length of hospital stay (LOS). Any comorbidity scored using the CCI or HCT-CI (score > 0) was associated with an increased number of organ systems with serious toxicity (at least grade 2 toxicity using the Seattle criteria), an increased total sum of toxicity grades for all organs, and prolonged LOS. An mPAM score > or = 24 was associated with increased LOS. When considering autologous HSCT for a patient with MM, assessment of comorbidities using the CCI or HCT-CI may assist in predicting the risk of transplantation-related toxicity as an adjunct to physician judgment and patient preference.

Reduced hemoglobin on day of peripheral blood progenitor cell collection is associated with low graft content of vascular progenitors and increased toxicity after autologous hematopoietic stem cell transplantation.

BACKGROUND: Tissue damage after hematopoietic stem cell transplantation (HSCT) occurs as a result of high-dose chemotherapy and radiation. The aim was to determine the importance of pretransplant anemia on toxicity and red blood cell (RBC) transfusion requirements after autologous HSCT. STUDY DESIGN AND METHODS: A total of 350 patients undergoing autologous HSCT were included in the analysis. Patient factors and pretransplant laboratory values of possible relevance were assessed in multivariate regression analysis. RESULTS: Reduced hemoglobin (Hb) on the first day of peripheral blood progenitor cell (PBPC) collection was significantly associated with increased organ toxicity after HSCT, as measured by the Seattle criteria. Lower Hb levels at baseline before transplantation, but not at PBPC collection, were significantly associated with increased RBC transfusion requirements. In a second cohort of 28 patients, higher Hb levels on the day of PBPC collection were significantly associated with increased levels of endothelial-like vascular progenitor cells in PBPC grafts. CONCLUSION: Our observations suggest that higher Hb levels on the day of PBPC collection may be a marker of reduced toxicity associated with HSCT and increased vascular progenitors in PBPC collections. Further, baseline anemia before transplant may reflect an unfavorable hematopoietic microenvironment that leads to increased RBC transfusion requirements.