Autologous Transplant Patients Research Articles

Results of Levofloxacin Prophylaxis Timing in Autologous and Allogeneic Stem Cell Transplantation: A Retrospective Cohort Study.

Background Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT).Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients. Methods We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis. Results Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times. Conclusion Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.

A Deeper Depth of Response After Salvage Therapy Improves Outcomes of Autologous Stem Cell Transplantation in Relapsed Lymphoma and the Feasibility of Non-controlled Rate Freezing of Peripheral Blood Stem Cells.

Background High-dose chemotherapy followed by autologous stem cell transplantation is considered a standard treatment approach for patients with relapsed Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL). The goal of autologous stem cell transplant in relapsed lymphoma is to achieve long-term disease control, i.e., cure, in contrast to disorders like multiple myeloma, where it only prolongs the duration of remission, progression-free survival, and improves the quality of life. Published outcomes of high-dose therapy and ASCT and the impact of different factors affecting survival in low- to middle-income countries are very limited. Our study analyzed all the autologous stem cell transplants performed in our center over a six-year period to ascertain engraftment, responses, outcomes, and variables that may have impacted transplant outcomes. Methods We conducted a retrospective study including 76 patients from January 2015 to December 2020. Data were retrieved from electronic medical records at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results Out of a total of 82 autologous transplant patients, 76 were eligible for the study, out of which 50 (66%) had HLand 26 (34%) had NHL. The median age was 29 years (range 18-53) and 29 years (range 20-45) for HL and NHL, respectively. The male-to-female ratio was 5:2 and 4:1 for HL and NHL, respectively. The majority had advanced-stage disease, 85% in HL and 75% in NHL. The minimum cell dose infused was 2.5 million CD34+ cells/kg. Median days to platelets and ANC engraftment were 14 and 11 days, respectively. The 30-day transplant-related mortality was 8.9% and 7.4% in HL and NHL, respectively. The 100-day mortality was 15.2% and 11% in HL and NHL, respectively. The two-year disease-free survival (DFS) and overall survival (OS) were 83% and 83%, respectively, in HL patients. The two-year DFS and OS were 78% and 85%, respectively, in NHL patients. Conclusion High-dose therapy and autologous stem cell transplantation in low- to middle-income countries are limited to relatively younger patients, potentially curative conditions such as lymphoma, and predominantly after achieving a complete response to salvage therapy due to limited resources. Due to these factors, our study shows excellent response rates and survival outcomes compared to internationally published data. Engraftment was also excellent and comparable to published data despite the non-controlled rate freezing of peripheral blood stem cells.

A comparison of GIT toxicity of the BEAM and TEAM conditioning before autologous transplantation in patients with lymphomas

A comparison of GIT toxicity of the BEAM and TEAM conditioning before autologous transplantation in patients with lymphomas

Gut Microbiome Faecalibacterium Abundance in Patients with Plasma Cell Disorders Undergoing Autologous Hematopoietic Stem Cell Transplant Is Associated with Progression Free Survival

Background: Different aspects of the gut microbiota (GM), including diversity, abundance, and functionality, have been linked to the development, progression, response, and adverse events to therapy in plasma cell neoplasms (PCN). The primary goal of this study was to further investigate the relationship between the composition of the GM, focusing on the genus Faecalibacterium that contains the most common anaerobic commensal bacterium in the GM ( Faecalibacterium prausnitzii), and clinical outcomes of patients with PCN undergoing autologous hematopoietic stem cell transplant (HSCT). Methods: GM samples were collected prospectively between 2017 and 2021 at our institution as part of a phase III, randomized clinical trial including patients with malignant hematologic diseases undergoing either chemotherapy or transplant. Fecal samples were obtained at pre (baseline), mid (defined as at 1 week from baseline), and end (defined as at engraftment, absolute neutrophil count &amp;gt; 500 cells/mm 3) autologous HSCT and processed by 16S rDNA sequencing (V1-V3) using Illumina MiSeq to determine Faecalibacterium abundance at each prespecified time point. Progression free survival (PFS) and overall survival (OS) were computed via Kaplan-Meier estimate. Results: 83 evaluable patients underwent autologous HSCT for PCN, 54 (65%) as part of frontline therapy. 79 (95%) of the transplant recipients carried a diagnosis of Multiple Myeloma. Melphalan was used as the conditioning regimen, with 54 (65%) of the patients receiving a dose of 200 mg/m 2 (versus 140 mg/m 2). The median age of the patients was 64 (range, 31-79) years and 50 (60%) were men. With median time to follow up for survivors (n= 82, alive &amp;gt; 1 month post HSCT) of 32 (range, 0.7-61) months, the median PFS was 40 months and median OS was not reached. Faecalibacterium relative abundance was 3.5%, 1.7%, and 2% of the GM at pre, mid, and end transplant, respectively. Higher baseline Faecalibacterium abundance was significantly associated with superior PFS (n= 79) (HR= 0.92, p= 0.01) and OS (HR= 0.88, p= 0.008). Patients were partitioned into 2 groups, those with pre-transplant Faecalibacterium abundance above median and below median, to generate representative Kaplan-Meier curves for PFS (Figure 1). Greater reduction in Faecalibacterium abundance during transplant, and especially from pre to mid transplant, were significantly associated with worse PFS (n= 75) (HR= 1.08, p= 0.007; HR= 1.10, p= 0.004, respectively) and OS (HR= 1.09, p= 0.021; HR= 1.09, p= 0.04, respectively). There was no significant relationship between Faecalibacterium abundance and PFS at mid (n= 83) (HR= 1, p= 1), end (n= 83) (HR= 1.01, p= 0.7), or notably mid to end transplant (n= 75) (HR= 1, p= 0.9). Levels of the bacteria also did not associate with OS from mid to end transplant (n= 75) (HR 1.01, p= 0.8). Conclusions: Our study indicated that Faecalibacterium abundance in the GM changed rapidly early after autologous HSCT in patients with PCN likely due to melphalan administration. Higher baseline levels and smaller reduction in Faecalibacterium abundance predicted superior PFS. Further follow up with more mature data is needed to confirm OS associations. These findings support the need for further investigation into the role of GM and possible interventions to modify GM to improve outcomes to autologous transplant in patients with PCN.

Survival of Hematopoietic Stem Cell Transplantation in the National Institute of Neoplastic Diseases, Lima-Perú between 2012 to 2022: 10 Years of Experience

Introduction: Hematopoietic stem cell transplantation (HSCT) is part of standard treatment in a great number of hematologic malignancies and some solid tumors. The National Institute of Neoplastic Diseases (INEN) started the HSCT program in 2012, performing over 600 HSCT so far. In this study, we report the overall survival (OS) at 5 years of patients who undergone this procedure in our institution through 10 years of experience. Methods: We analyzed retrospectively the survival of all patients admitted to the HCST program at INEN between 2012 and 2022. Clinical and pathological data were collected from the medical records and the unit's transplant patient registry. The OS was determined through the Kaplan-Meier method and the comparisons of survival curves were performed using the log-rank or Breslow test. Results: During the study period, a total of 647 transplants were performed. The median age was 39 years (range: 1 - 70), 73.4% of patients were between 18 and 60 years, and 57.1% were men. Most transplants (n = 591, 91.3%) were performed in the adult population and 8.6% (n = 56) in pediatric population. According to the type of transplant, 68% (n=440) were autologous and 32% (n=207) allogeneic from related donor. The most frequent diagnosis were acute leukemia (n = 221, 34.2%), multiple myeloma (n = 190, 29.3%), non-Hodgkin lymphoma (n = 105, 16,2%; of these, 22 were T- cell lymphomas), Hodgkin lymphoma (n = 69, 10.7%) and germinal cell tumor (n = 33, 5.1%); in the pediatric population, leukemia was the most common diagnosis (66.1%). The median follow-up of the patients was 3.7 years (95% CI: 3.4, 3.9), 25.2% (n = 163) of the patients died due to disease progression. The median overall survival (OS) for the entire cohort was not reached and the OS rate at 5 years was 68.3%. The 5-year OS rate by transplant subtype was 53.9% and 75.3% (p &amp;lt; 0.001) for allogeneic and autologous transplants, respectively; and according to the pathology, the patients who had a better 5-year OS were HL (87.5%) and NHL (77.5%), while in leukemias it was 56.1%. Survival by age group (&amp;lt;40 vs &amp;gt;40) and sex (female vs. male) did not present a significant difference (p &amp;gt; 0.05). Conclusions: The survival of the transplanted patients was similar to that reported in other series. Leukemia was the most frequent hematological malignancy admitted to the HSCT program. HL and NHL were the malignant tumors with the highest survival rates at 5 years. Nearly a third of transplants were allogeneic, all from matched related donors. HSCT in our series has shown an improvement in OS at 5 years in both autologous and allogeneic transplant patients compared to non-transplanted patients, according to international reports.

Hematopoietik Kök Hücre Nakli Türüne ve Nakil Öncesi Mevcut Polifarmasiye Bağlı Olarak İlaç-İlaç Etkileşimi Farklılıkları

Introduction: Drug drug interactions can effect the success of stem cell transplantation process. Therefore, analyzing the risk of these interactions would be helpful for practitioners. This study was conducted to identify drug-drug interactions in allogeneic and autologous stem cell transplantation patients before and after transplantation. &#x0D; Methods: Patients who underwent allogeneic stem cell transplantation and autologous stem cell transplantation were included in the study. Patients’ treatment sheets were collected ten days before transplantation day, on the transplantation day, and ten days after transplantation day. Drug-drug interactions were analyzed by using four drug-drug interaction checking databases.&#x0D; Results: 50 patients from both transplantation types were included. The mean ages for allogeneic and autologous transplants were 42.4 and 51.8, respectively. 52% of allogeneic transplants and 28% of autologous transplants were on ≥5 drugs at tenth day before transplantation. The means of interactions in allogeneic and autologous stem cell transplantation patients were 75.42 and 43.62, respectively. The detection of at least one contraindicated interaction in allogeneic and autologous transplant patients were 94% and 92%, respectively. In 48% of allogeneic transplants and 36% of autologous transplants, two or more contraindicated interactions were detected.&#x0D; Conclusion: Allogeneic stem cell transplantation patients experienced almost two times more drug-drug interactions than autologous stem cell transplantation patients. Transplantation type, being in the pre and post-transplantation period and the drug number at the beginning of the transplantation process matter in terms of the number of drug-drug interactions. Identifying interactions in terms of transplantation type and existing medications is very important.

Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma.

We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded with full-length survivin (Ad-S), with mutations neutralizing its antiapoptotic function, could safely generate an immune response and deepen clinical responses when administered before and after autologous stem cell transplant (ASCT) for multiple myeloma. This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed multiple myeloma not having achieved complete response with induction, given 7 to 30 days prior to stem cell collection and 20 to 34 days after ASCT. Anti-survivin antibodies and CD4+ and CD8+ specific T cells were quantified. A total of 14 patients were treated and 13 included in the primary efficacy analysis. No serious adverse events were attributed to DC:Ad-S vaccine. Detectable anti-survivin antibodies increased from baseline in 9 of 13 (69%) patients, and 11 of 13 (85%) mounted either a cellular or humoral immune response to survivin. Seven patients had an improved clinical response at day +90, all of whom had mounted an immune response, and 6 of 7 patients remain event-free at a median follow-up of 4.2 years. Estimated progression-free survival at 4 years is 71% (95% confidence interval, 41-88). Two doses of DC:Ad-S, one given immediately before and another after ASCT, were feasible and safe. A high frequency of vaccine-specific immune responses was seen in combination with durable clinical outcomes, supporting ongoing investigation into the potential of this approach. See related commentary by Dhodapkar, p. 4524.

POSTER: MM-610 Impact of Induction Therapy on the Mobilization and Engraftment of Peripheral Blood Hematopoietic Progenitors for Autologous Transplantation in Patients With Multiple Myeloma. Experience of the University Hospital of Salamanca (Spain)

POSTER: MM-610 Impact of Induction Therapy on the Mobilization and Engraftment of Peripheral Blood Hematopoietic Progenitors for Autologous Transplantation in Patients With Multiple Myeloma. Experience of the University Hospital of Salamanca (Spain)

MM-610 Impact of Induction Therapy on the Mobilization and Engraftment of Peripheral Blood Hematopoietic Progenitors for Autologous Transplantation in Patients With Multiple Myeloma. Experience of the University Hospital of Salamanca (Spain)

MM-610 Impact of Induction Therapy on the Mobilization and Engraftment of Peripheral Blood Hematopoietic Progenitors for Autologous Transplantation in Patients With Multiple Myeloma. Experience of the University Hospital of Salamanca (Spain)

CD19/CD22 chimeric antigen receptor (CAR) T-cell cocktail therapy following autologous transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma on 18F-FDG PET/CT: a case description.

CD19/CD22 chimeric antigen receptor (CAR) T-cell cocktail therapy following autologous transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma on 18 F-FDG PET/CT: a case description

Applying a risk prediction model for bloodstream infection in a febrile, nonseverely neutropenic cohort of pediatric stem cell transplant patients.

The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC]≥500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT-specific data are limited. All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c-statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model(EsVanAlloSCT), was developed and internally validated. For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p< .01). All versions of the EsVan model performed well for the overall SCT cohort (c-statistics, 0.759-0.795). The EsVan models performed better for the autologous episodes (c-statistics, 0.869-0.881) than the allogeneic SCT episodes (c-statistics, 0.678-0.717). The new allogeneic transplant-specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c-statistic of 0.792 (bootstrap-corrected, 0.750). The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.

174 - Enteral Nutrition Leads Less Severe Gastrointestinal Mucositis and Less Days of Nutritional Support As Compared to Parenteral Nutrition Among Autologous Transplant Patients in a Randomized Study

174 - Enteral Nutrition Leads Less Severe Gastrointestinal Mucositis and Less Days of Nutritional Support As Compared to Parenteral Nutrition Among Autologous Transplant Patients in a Randomized Study

Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant

ObjectiveMucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. MethodsA total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann–Whitney U and CFA, respectively. ResultsOMDQ-Mal demonstrated high internal consistency (α ​= ​0.874). Test–retest reliability between paired days were moderate to excellent (95% CI ​= ​0.676–0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ ​= ​0.503–0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708–0.952; composite reliability 0.879–0.974; average variant extracted 0.710–0.841; and heterotrait–monotrait ratio 0.528 established the convergent and divergent validity. ConclusionsIn conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

Cost-Effectiveness Analysis of Motixafortide Versus Plerixafor in Stem Cell Mobilization for Autologous Transplantation in Patients with Multiple Myeloma

Introduction: The Phase 3 GENESIS trial (NCT03246529) compared the efficacy and safety of motixafortide and granulocyte-colony stimulating factor (M+G) to placebo + G (PBO+G) for the mobilization of hematopoietic stem cells (HSCs) prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Compared with PBO+G, M+G significantly increased the proportion of patients who were able to successfully mobilize ≥6x106 CD34+ cells/kg for ASCT within 2 apheresis days (92.5% vs. 26.2%; p<0.0001). In a cost-effectiveness model (CEM) based on the GENESIS trial, M+G yielded additional quality-adjusted life years (QALYs) and cost savings relative to G alone from a United States (US) healthcare payer perspective (Lamotte et al. (2022) Value Health 25(7): S346). Plerixafor + G (P+G) is also used for HSC mobilization prior to ASCT in patients with MM. To date, M+G and P+G have not been directly compared in head-to-head trials; therefore, the relative efficacy and cost effectiveness of these therapies is currently unknown. Methods: The Bucher method was used to assess the relative efficacy of M+G in the GENESIS trial and P+G in the Phase 3 AMD-3102 trial (NCT00103662), with the PBO+G arms of both trials used as a common comparator. Risk ratios (RRs) were derived for binary trial endpoints (i.e., proportion with mobilization of ≥6x106 CD34+ cells/kg within 1-4 apheresis days, successful engraftment, use of rescue therapy, proportion who underwent ASCT, incidence of serious adverse events [SAEs]) and mean differences were derived for continuous trial endpoints (i.e., number of study drug doses received, frequency and amount of G doses, and number of apheresis sessions). The RRs were then used to update the CEM to compare the cost effectiveness of M+G and P+G from a US healthcare payer perspective over a lifetime horizon; model assumptions and sources for unit costs and quality of life scores were unchanged from the previously published CEM. Results: The mean age at baseline was 59-60 years in GENESIS and 58 years in AMD-3102; heterogeneity was observed for the mean time since diagnosis (6-7 vs. 11-12 months), prior radiotherapy (10%-11% vs. 27%-31%), and the ethnic and sex distribution of the PBO+G arms (White: 95% vs. 83%; males: 57% vs. 70%). Notably, prior lenalidomide use was markedly lower in AMD-3102 (<10%) than in GENESIS (70%), which likely contributed to the higher mobilization rates in the AMD-3102 PBO+G arm than in the GENESIS PBO+G arm. In the Bucher analysis, healthcare resource utilization (HRU) outcomes significantly favored M+G during primary mobilization, including less frequent administration of G (mean difference [MD]: -0.97; 95% CI -1.43, -0.50; p=0.0001), lower G doses (MD: -920 mcg; 95% CI -1,368, -471; p=0.0001), and fewer apheresis sessions (MD: -0.98; 95% CI -1.34, -0.63; p<0.0001) (Table 1). The proportion of patients with successful mobilization of ≥6x106 CD34+ cells/kg within 1 apheresis day was significantly greater with M+G (88.8%) than with P+G (54.2%; RR 2.97; 95% CI 1.08, 8.17; p=0.0341). Similar results were observed between groups for other outcomes, including ASCT rates (RR 1.06; 95% CI 0.93, 1.21; p=0.4124), engraftment durability by 100 days (RR 0.98; 95% CI 0.87, 1.11; p=0.7894), and SAE rate (RR 2.36; 95% CI 0.26, 21.05; p=0.4521); analyses were limited to publicly available data for P+G, and were not feasible for the use of rescue therapy because of insufficient sample size. In the cost-effectiveness analysis, M+G was dominant to P+G over a lifetime horizon, resulting in additional QALYs (+0.0358) and lower total costs (-$17,378 USD; Table 2) as per base case deterministic results. The key cost drivers were the probability of successful transplantation, long-term maintenance costs, and the time to engraftment in poor mobilizers. In a probabilistic sensitivity analysis, M+G was dominant in 66% of simulations and 92% cost effective at a WTP threshold of $50,000 per QALY. Conclusions: The results of this analysis show that the use of M+G was associated with significantly lower HRU relative to P+G for the mobilization of HSCs prior to ASCT in patients with MM, as well as significantly greater successful mobilization of ≥6x106 CD34+ cells/kg within 1 apheresis day. Cost-effectiveness analysis results showed that M+G was dominant to P+G, yielding additional QALYs and net cost savings over a lifetime horizon from a US healthcare payer perspective. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Delayed Neutrophil Engraftment in Autologous Transplant Patients with Very High CD34+ Cell Collections in a Single Apheresis

Background: The number of CD34+ cells infused during autologous hematopoietic stem cell transplantation (auto-HSCT) is the most important determinant of the speed of engraftment and neutrophil recovery. Increasing the infused CD34+ cell doses results in faster neutrophil recovery, but infusion of more than 5-10 x 106/kg CD34+ cells typically does not hasten engraftment any further. In contrast, we have noticed cases of delayed engraftment when the number of CD34+ cells collected has been extraordinarily high. We report a single center experience of engraftment in auto-HSCT patients with very high CD34+ cell numbers collected in a single apheresis session (typically 20 L blood volume). Methods: Utilizing the database of the Stem Cell Transplantation and Cell Therapy Program and the Mathews Center for Cellular Therapy, we studied apheresis and engraftment data on patients undergoing auto-HSCT for hematologic malignancies at Northwestern Memorial Hospital from January 2000 through June 2022. Inclusion criteria were age ≥18 years, ≥20 x 106/kg CD34+ cells collected in a single aphaeresis session, and available neutrophil engraftment data. Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 109/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery. Fisher's exact test of independence was utilized to determine the statistical significance of the difference between variables. Results: We identified 214 patients with a yield of ≥20 x 106/kg CD34+ cells in one apheresis session. Patients were divided into two groups depending on the number of CD34+ cells collected; ≥20 but <50 (group A; n=93) and ≥50 (group B; n=121). Group A had a median collection of 31.1 x 106/kg CD34+ cells and group B had 66.8 x 106/kg. For group A, the median time to neutrophil recovery was 12 days, compared with 11 days for group B. Zero out of 93 patients in group A had delayed engraftment compared with 7 of the 121 patients (6%) in group B (P=0.022). All 7 patients with delayed engraftment were mobilized with single-agent granulocyte-colony stimulating factor. Four patients had myeloma, 2 acute promyelocytic leukemia (APL), and 1 Waldenstrom's macroglobulinemia (WM) (Table 1). Patients with myeloma and WM (all in first partial remission) received high-dose melphalan conditioning and patients with APL (both in second complete remission) received busulfan-cyclophosphamide. For the 7 patients with delayed engraftment, the median number of CD34+ cells infused was 14.5 x 106/kg (range 9.5-19.6) with a median time to neutrophil engraftment of 24 days (range 20-38). Conclusions: We describe an uncommon phenomenon of delayed engraftment in some patients with very high CD34+ cell yields in a single apheresis. Additional studies on stored autologous stem cells are needed to elucidate the cause of this peculiar finding. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Survival and response deepening after autologous transplantation in patients with multiple myeloma in Chile

ABSTRACT Background Autologous hematopoietic stem cell transplantation (ASCT) is the standard of care in candidate patients with newly diagnosed multiple myeloma. In Chile, its indication has been expanding as have centers dedicated to this type of therapy. Here, we present the results of the first 50 patients from a Chilean reference center. Methods This was a retrospective analytical study of 50 patients referred to the Arturo López Pérez Foundation to receive ASCT. Patients newly diagnosed or on subsequent lines of treatment were allowed. As primary objectives, the deepening of response with ASCT and subsequent results on overall survival and progression-free survival were analyzed. Results Among 50 patients with a median follow-up of 24 months, ASCT managed to deepen responses going from at least very good partial response of 57.4%–82.5% (p = .01); complete response increased from 27.6% to 52.5% (p = .02). In turn, a median progression-free survival (PFS) of 39 months was estimated and the median overall survival was not reached. The most important factor predicting PFS is measurable residual disease. Conclusions ASCT is an effective strategy for prolonged progression-free survival and deepening responses. Public–private collaboration is a crucial element in reducing the gaps in access to this type of complex but highly effective therapy.

USING 6-MINUTE WALKING DISTANCE AND FRAILTY MEASURES TO PREDICT RISK OF POSTSTEM CELL TRANSPLANT PULMONARY COMPLICATIONS AND MORTALITY

SESSION TITLE: Unique Uses of Pulmonary Function TestsSESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/19/2022 11:15 am - 12:15 pmPURPOSE: Pulmonary complications occur frequently after hematopoietic stem cell transplant (HCT) and are associated with a high mortality rate. Abnormalities in pulmonary function tests (PFTs) have been associated with higher non-relapse mortality and increased risk of post-HCT pulmonary complications. However, standard PFTs only provide limited physiologic assessments of pulmonary function. More comprehensive functional evaluation may provide greater insight into post-transplant pulmonary complication risk. In this project, we evaluated a simple noninvasive cardiopulmonary test (6-minute-walk test) alongside frailty testing (grip strength and gait speed) to determine the risk of post-HCT pulmonary complications and mortality.METHODS: We are enrolling adult patients (>18 year old) from July 2021 to June 2022 undergoing pre-HCT evaluation at Mayo Clinic Rochester and presenting for their transplant pulmonary function tests. After informed consent, patients undergo 6-minute walk test (6MWT), grip strength and gait speed test. Additional demographic data, PFT results and clinical course after transplant for 1 year will be obtained, including incidence of pulmonary complications and need for ICU admission and mechanical ventilation.RESULTS: As of 3/10/2022, 88 patients have been enrolled and 62 patients (70.5%) have undergone HCT. Among the 62 transplanted patients, 49 (79.0%) underwent autologous transplant, and 13 (21.0%) underwent allogeneic transplant. The mean age was 57.1 years, and the most common indication for transplant was multiple myeloma (43.4%). For autologous transplant patients, the most common conditioning regimen was melphalan 200 mg/m2 (62.1%). For allogeneic transplant patients, the most frequent conditioning regimen was fludarabine and melphalan (53.8%). The average 6-minute-walk test (6MWT) distance was 1580.5 feet or 87.9% predicted of healthy adults, and mean gait speed was 1.3 m/s (normal ≥0.8 m/s). Among autologous transplant patients, 26.5% had abnormal grip strength and 18.4% had abnormal 6MWT distance. Among allogeneic transplant patients, 46.2% had abnormal grip strength and 23.1% had abnormal 6MWT distance. Six pulmonary complications requiring hospitalization have occurred. Out of the 6 patients, 2 had abnormal grip strength and 1 had abnormal 6MWT distance. The incidence of non-relapse mortality was 0% after a median follow up of 92 days (range 3-156 days).CONCLUSIONS: Frailty measures such as 6MWT distance and hand grip strength can be abnormal among patients undergoing HCT. The study is still ongoing to determine the association between pre-transplant functional status and post-transplant pulmonary complication risk and mortality.CLINICAL IMPLICATIONS: The results from this study would be additions for pre-HCT transplant risk assessment to better inform clinicians and patients and identify at risk patients who can benefit from more rigorous post-transplant monitoring.DISCLOSURES: No relevant relationships by Mehrdad HefaziNo relevant relationships by William HoganNo relevant relationships by Cassie KennedyNo relevant relationships by Abdul WahabNo relevant relationships by Hemang YadavNo relevant relationships by Zhenmei Zhang SESSION TITLE: Unique Uses of Pulmonary Function Tests SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Pulmonary complications occur frequently after hematopoietic stem cell transplant (HCT) and are associated with a high mortality rate. Abnormalities in pulmonary function tests (PFTs) have been associated with higher non-relapse mortality and increased risk of post-HCT pulmonary complications. However, standard PFTs only provide limited physiologic assessments of pulmonary function. More comprehensive functional evaluation may provide greater insight into post-transplant pulmonary complication risk. In this project, we evaluated a simple noninvasive cardiopulmonary test (6-minute-walk test) alongside frailty testing (grip strength and gait speed) to determine the risk of post-HCT pulmonary complications and mortality. METHODS: We are enrolling adult patients (>18 year old) from July 2021 to June 2022 undergoing pre-HCT evaluation at Mayo Clinic Rochester and presenting for their transplant pulmonary function tests. After informed consent, patients undergo 6-minute walk test (6MWT), grip strength and gait speed test. Additional demographic data, PFT results and clinical course after transplant for 1 year will be obtained, including incidence of pulmonary complications and need for ICU admission and mechanical ventilation. RESULTS: As of 3/10/2022, 88 patients have been enrolled and 62 patients (70.5%) have undergone HCT. Among the 62 transplanted patients, 49 (79.0%) underwent autologous transplant, and 13 (21.0%) underwent allogeneic transplant. The mean age was 57.1 years, and the most common indication for transplant was multiple myeloma (43.4%). For autologous transplant patients, the most common conditioning regimen was melphalan 200 mg/m2 (62.1%). For allogeneic transplant patients, the most frequent conditioning regimen was fludarabine and melphalan (53.8%). The average 6-minute-walk test (6MWT) distance was 1580.5 feet or 87.9% predicted of healthy adults, and mean gait speed was 1.3 m/s (normal ≥0.8 m/s). Among autologous transplant patients, 26.5% had abnormal grip strength and 18.4% had abnormal 6MWT distance. Among allogeneic transplant patients, 46.2% had abnormal grip strength and 23.1% had abnormal 6MWT distance. Six pulmonary complications requiring hospitalization have occurred. Out of the 6 patients, 2 had abnormal grip strength and 1 had abnormal 6MWT distance. The incidence of non-relapse mortality was 0% after a median follow up of 92 days (range 3-156 days). CONCLUSIONS: Frailty measures such as 6MWT distance and hand grip strength can be abnormal among patients undergoing HCT. The study is still ongoing to determine the association between pre-transplant functional status and post-transplant pulmonary complication risk and mortality. CLINICAL IMPLICATIONS: The results from this study would be additions for pre-HCT transplant risk assessment to better inform clinicians and patients and identify at risk patients who can benefit from more rigorous post-transplant monitoring. DISCLOSURES: No relevant relationships by Mehrdad Hefazi No relevant relationships by William Hogan No relevant relationships by Cassie Kennedy No relevant relationships by Abdul Wahab No relevant relationships by Hemang Yadav No relevant relationships by Zhenmei Zhang

Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma.

Autologous stem cell transplantation is the standard procedure for multiple myeloma and the grafts are usually cryopreserved. Previous studies reported advantages in the use of fresh peripheral blood stem cells (PBSC) autotransplantation compared to cryopreservation of the grafts. This study compared the transplant-related outcomes of two graft preservation methods: fresh storage (4°C/72 h) and cryopreservation (-80°C). We performed an analysis of 45 patients with multiple myeloma under autotransplantation (17 fresh and 28 cryopreserved) from 2017 to 2021. Fresh PBSC were maintained in the refrigerator for three days in a concentration up to 300 × 103 TNC/μL. Cryopreserved PBSC were concentrated by plasma reduction after centrifugation (950 g/10min/4°C) and an equal volume of cryoprotection solution was added for a final concentration of 300 × 103 TNC/μL, 5% DMSO, 6% hydroxyethyl starch, and 3% human albumin. Neutrophil engraftment was significantly faster with fresh PBSCs (10 vs. 11.5 days, p=0.045). Adverse effects were more common in cryopreserved PBSC transplantation (75% vs. 35.3% patients; p=0.013). Post transplantation hospital stay was 20 and 22 days for fresh and cryopreserved PBSCs respectively (p=0.091). There was no difference in platelet engraftment time (10.5 days for both; p=0.133), number of antibiotics used after transplantation (3 for fresh and 2.5 for cryopreserved; p=0.828), days of antibiotic use after transplantation (12.2 days for fresh and 13.3 days for cryopreserved, p=0.579), and overall survival (p=0.736). The infusion of fresh PBSC refrigerated for up to three days is effective and safe for autologous transplantation in patients with multiple myeloma, which is a useful alternative to cryopreserved PBSC.

P-009: Busulfan and cyclophosphamide as a conditioning regimen for autologous transplantation in patients with multiple myeloma after treatment with proteasome inhibitors and/or immunomodulatory drugs

P-009: Busulfan and cyclophosphamide as a conditioning regimen for autologous transplantation in patients with multiple myeloma after treatment with proteasome inhibitors and/or immunomodulatory drugs

Elevated islet prohormone ratios as indicators of insulin dependency in auto-islet transplant recipients

Pancreatic islet transplantation has therapeutic potential in type 1 diabetes and is also an established therapy in chronic pancreatitis. However, the long-term transplant outcomes are modest. Identifying indicators of graft function will aid the preservation of transplanted islets and glycemic control. We analyzed beta cell prohormone peptide levels in a retrospective cohort of total pancreatectomy autologous islet transplant patients (n = 28). Proinsulin-to-C-peptide (PI/C) and proIAPP-to-total IAPP (proIAPP/IAPP) ratios measured at 3 months post-transplant were significantly higher in patients who remained insulin dependent at 1 year follow-up. In an immuno-deficient mouse model of human islet transplantation, recipient mice that later became hyperglycemic displayed significantly higher PI/C ratios than mice that remained normoglycemic. Histological analysis of islet grafts showed reduced proportional insulin- and proinsulin-positive area, but elevated glucagon-positive area in grafts that experienced greater secretory demand. Increased prohormone convertase 1/3 was detected in glucagon-positive cells, and glucagon-like peptide 1 (GLP-1) area was elevated in grafts from mice that displayed hyperglycemia or elevated plasma PI/C ratios, demonstrating intra-islet incretin production in metabolically challenged human islet grafts. These data indicate that in failing grafts, alpha cell prohormone processing is likely altered, and incomplete beta cell prohormone processing may be an early indicator of insulin dependency.