Autologous Patients Research Articles

Autologous Breast Reconstruction Success Rates in Hypercoagulable Patients.

Hypercoagulable disorders may adversely affect microsurgical outcomes, including increased flap failure and complication rates. Outcomes specific to autologous breast reconstruction are not well described. A retrospective review was performed of autologous breast reconstructions between 2009 and 2020. Patients with either a thrombophilic disorder (TD) diagnosis or a previous thrombotic event (TE) were identified. The analysis compared perioperative complications and flap success rates. In this series, 23 patients with a TD underwent 39 flaps, and 78 patients who had experienced a TE underwent 126 flaps, compared with 815 control patients, who underwent 1300 flaps. In logistic regression models, a TD diagnosis was an independent predictor of early total flap loss [OR, 8.42 (95% CI, 1.59 to 44.47); P = 0.01], late partial flap loss [OR, 3.9 (95% CI, 1.0 to 15.22); P = 0.05], and delayed healing [OR, 2.26 (95% CI, 1.02 to 5.04); P = 0.04]. TE history trended toward an association only with late partial flap loss ( P = 0.057). Flap salvage rates (25%) and flap success rates (92.3%) were statistically lower in patients with a TD but normal in patients who had experienced a TE. Microsurgical breast reconstruction is a reasonable option for patients with hypercoagulation disorders. No increased risk of flap complications was associated with a previous TE; however, TDs carried increased risk. Risk, II.

Influence of Acute and Chronic Graft-Versus-Host Disease on Persistence of Antibodies against Measles, Mumps, Rubella and Varicella in the First Year after Autologous or Allogeneic Hematopoietic Stem Cell Transplantation

Patients after hematopoietic stem cell transplantation (HSCT) are vulnerable to infections due to severe immunosuppression. Live-attenuated vaccines are contraindicated for two years after HSCT. The aim of this study was to assess the persistence of antibodies against measles, mumps, rubella and varicella in the first year after HSCT. Forty patients undergoing autologous (n = 12) or allogeneic (n = 28) HSCT were included in this study. Specific IgG antibodies to measles, mumps, rubella and varicella virus in serum samples were assessed by the LIAISON XL, a fully automated chemiluminescence analyzer, at seven different time points starting one week before HSCT and up to 12 months after HSCT. At baseline, before HSCT, most patients showed antibodies against measles (100%), mumps (80%), rubella (97.5%) and varicella (92.5%). Although titers declined over time, most patients retained antibodies against measles (92.5%), mumps (62.5%), rubella (87.5%) and varicella (85%) up to 12 months after HSCT. There was no significant difference between patients with and without GvHD concerning persistence of antibody titers. Significantly higher varicella titers were detected in autologous patients compared to patients with chronic GvHD. Considering that live-attenuated vaccines should not be administered during the first year after HSCT, the persistence of antibodies against these diseases is relevant.

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.

Extramedullary relapse of Immunoglobulin A-kappa myeloma manifesting as plasmacytoma of the pleura without bone marrow involvement and following autologous bone marrow transplant: a case report

BackgroundRecurrence of multiple myeloma is among the most challenging issues for patients and treating physicians reported after autologous stem cell transplantation. However, extramedullary involvement after chemotherapy and transplantation has been rarely reported, especially as pleural manifestations. Protein electrophoresis indicated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case.Case presentationA 48-year-old middle-eastern man was referred to our clinic with cough, dyspnea, fever, and left side pleural effusion. A year after chemotherapy and autologous bone marrow transplantation, the patient presented with features in favor of pleural relapse, without bone marrow involvement. Protein electrophoresis demonstrated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case. The patient was effectively treated with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide with no notable adverse effects.ConclusionPhysicians should be aware of various presentations of multiple myeloma relapse, especially in autologous stem cell transplantation patients. Atypical and unique presentations such as the pleural involvement warrant further reporting of evidence to provide early management and treatment options.

Examining Racial Inequities in Implant-based Breast Cancer Reconstruction

Objective: Significant racial disparities persist among implant-based breast cancer reconstruction patients. Proper patient selection remains a large consideration in breast reconstruction. There is paucity of data highlighting differences in implant-based reconstruction outcomes by race. To expand on this knowledge, this study compares three patient risk factors: obesity, diabetes, and smoking, with subsequent complication rates between racial cohorts who received implant-based breast reconstruction. Methods: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was performed on patients receiving implant-based breast reconstruction determined by primary or concurrent CPT codes 19340, 19342, 19357, and 19380 from 2016-2019. Patients were stratified by race, then assessed for preoperative differences and postoperative outcomes. Patients with an unknown/not reported race were excluded from the analysis. All categorical variables were analyzed using chi-squared or Fisher’s exact test. Significance was determined using a p-value of 0.05. Results: A total of 30,749 patients met the inclusion criteria for our study, 84.3% of which are White. African American, Indigenous or Alaskan Native, and Native Hawaiian or Pacific Islander patients were significantly more likely to present with a BMI over 30 kg/m2 (p<0.0001) than Asian and White patients. African American, Native Hawaiian or Pacific Islander, and Asian patients are significantly more likely to have diabetes (p<0.0001; 14.29%, 11.88%, and 7.77% respectively) than White patients (5.57%). African American patients were the most likely to be active smokers compares to Asian patients (p<0.0001; 9.34% and 4.08% respectively). In terms of complications, Indigenous patients had significantly higher prevalence of infection, reoperation, and readmission compared all other racial groups. African American patients were significantly more likely to encounter wound dehiscence compared to Asian patients (p=0.0075; 1.08% vs. 0.24%). Conclusion: Non-White races had higher rates of obesity, diabetes, and smoking and that correlated to the higher rates of post-operative complications. Further research is needed to investigate if similar preoperative risk factors are also reflected in autologous breast cancer reconstruction patients and if race is a determinant in patient outcomes post breast cancer reconstruction. Corresponding Author: Neej Patel, 411 E 2nd St Apt#112 Flint, MI 48503, [email protected], 7343064487

Quality of Life in Breast Reconstruction Patients after Irradiation to Tissue Expander: A Propensity-Matched Preliminary Analysis.

Tissue expanders (TEs) are routinely placed as a first step in breast reconstruction for women who require postmastectomy radiation therapy (PMRT). The final reconstruction can then be performed with implants or conversion to autologous tissues. The purpose of this study was to compare patient-reported outcomes and surgical complications in autologous (ABR) versus implant-based breast reconstruction (IBR) patients following TE-PMRT. The authors performed a propensity score preliminary analysis (1:1 matching, no replacement) in patients undergoing ABR or IBR following TE-PMRT. Matched covariates included age, race/ethnicity, smoking status, body mass index, history of psychiatric diagnosis, and laterality of reconstruction. Outcomes of interest included complications and BREAST-Q scores for Satisfaction with Breasts, Physical Well-Being of the Chest, Sexual Well-Being, and Psychosocial Well-Being domains. Of 341 patients with TE-PMRT, a total of 106 patients were included in the matched analysis: 53 ABR patients and 53 IBR patients. ABR and IBR did not differ significantly in matched baseline, cancer, and surgical characteristics. ABR patients had higher scores for Satisfaction with Breasts (greater than the four-point minimal clinically important difference) at all postreconstruction time points compared with IBR patients ( P < 0.05). There were no significant postoperative differences in other BREAST-Q domains. The incidence of complications after definitive reconstruction did not differ significantly among cohorts. In this matched preliminary analysis, patients who underwent ABR following irradiation to a TE demonstrated superior satisfaction with breast scores compared with IBR patients. Higher powered matched studies are needed to improve shared decision-making for patients who require mastectomy and PMRT as part of their treatment. Therapeutic, III.

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

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54–64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.

Latissimus dorsi flap - the main force in breast reconstruction for breast tumor in Chinese population.

The latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction (BR) in China. We conducted this study to explore the current status of BR using LDF with/without implants. This study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) between 2000 and 2021. We analyzed 4918 patients who underwent postmastectomy BR, including 1730 patients (35.2%) with autologous flaps. LDF was used for BR in 1093 (22.2%) patients, and an abdominal flap was used in 637 (13.0%) patients. The proportion of LDFs used in autologous BR patients decreased each year and dropped to approximately 65.0% after 2013 due to the increased use of abdominal flaps. Among these patients, 609 underwent extended LDF (ELDF) BR, 455 underwent LDF BR with implants, and 30 received a LDF as a salvage flap due to previous flap or implant failure. Patients who underwent ELDF reconstruction were older and had a higher BMI than those who received a LDF with implants. There was no significant difference in the mean postoperative hospital stay, neoadjuvant chemotherapy rates, or adjuvant radiotherapy rates between the two groups. Major complications requiring surgical intervention occurred in 25 patients (2.29%). There was no significant difference in the incidence of major complications between the two groups (P=0.542). LDF breast reconstruction is a well-developed and safe procedure. The duration of postoperative hospitalization nor the incidence of major complications was affected by implant use.

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.

Impact of Prepectoral versus Subpectoral Tissue Expander Placement on Outcomes in Delayed-Immediate Autologous Patients Who Undergo Postmastectomy Radiation Therapy.

Delayed-immediate autologous (DIA) breast reconstruction is a safe and flexible operative strategy for patients undergoing postmastectomy radiation therapy (PMRT). Traditionally, tissue expanders (TE) are placed in the subpectoral position, but the development of acellular dermal matrix material has led to increased use of prepectoral placement strategies. Our aim was to compare the outcomes of both TE placement strategies in DIA patients who underwent PMRT and determine whether they experienced outcomes similar to those in non-PMRT patients. A retrospective analysis of four patient groups (314 total patients) who underwent DIA reconstruction from 2012 to 2019 was performed. Ninety-eight non-PMRT prepectoral (PP), 106 non-PMRT subpectoral (SP), 39 PMRT PP, and 71 PMRT SP patients were compared. Demographics, TE complications, flap complications, and the use of large inferior skin patches were analyzed. A significantly lower percentage of the PMRT PP cohort required large inferior skin patches (30.6% versus 55.7%; P < 0.05) and multiflap procedures (15.4% versus 47.9%; P < 0.001) than the PMRT SP cohort. PMRT ( P < 0.0001), SP placement ( P < 0.05), body mass index ( P < 0.05), autoimmune diseases ( P < 0.05), and bilateral mastectomy ( P < 0.001) were identified as factors predictive of patients requiring a large inferior patch by means of multivariable analysis. More SP patients experienced flap postoperative breast complications compared with PP patients (35.8% versus 12.2%; P < 0.0001). DIA patients who undergo PMRT will require more skin and flaps if SP TE placement is chosen over PP TE placement. Therapeutic, III.

Impact of Benzodiazepine Use on Length of Stay and 30-Day ED Visits among Hospitalized Hematopoietic Stem Cell Transplant Recipients.

This study assesses the impact of benzodiazepine (BNZ) use on length of stay (LOS) and 30-day emergency department (ED) visits after hematopoietic stem cell transplant (HSCT). Adult patients (18 years and older) who underwent an allogeneic or an autologous HSCT from 2015 to 2018 at the study site were included. Five multivariable models were used for both allogeneic and autologous HSCT: BNZ-naïve status, diazepam equivalent daily dosage (DEDD; 0 vs any), DEDD (excluding 0), ED visits, and LOS. BNZ-naïve autologous HSCT recipients were less likely to use any BNZs in the hospital (odds ratio [OR] 0.07, P < 0.001). If prescribed BNZs, then they used a lesser amount (incidence rate ratio 0.39, P < 0.001). BNZ-naïve autologous HSCT recipients were less likely to experience a 30-day ED visit (OR 0.17, P = 0.009). BNZ-naïve allogeneic HSCT recipients were also less likely to use any BNZ than previous users (OR 0.11, P = 0.014). Patient characteristics influenced BNZ naïvety, DEDD usage, LOS for autologous patients, and BNZ naïvety and DEDD for allogeneic patients. BNZ use resulted in increased 30-day ED visits after autologous HSCT. BNZ-naïve recipients were less likely to use BNZs during hospital stays; if they required BNZs, then it was in lower dosages.

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

Real World Favourable Experience of Haematopoietic Stem Cell Transplantation during Acute Coronavirus Disease 2019 in a Highly-Vaccinated Asian Population

Background Patients with high-risk haematological malignancies often progress and succumb to their disease without a timely haematopoietic stem cell transplantation (HCT). However, in patients undergoing HCT following acute Coronavirus disease 2019 (COVID-19) infection, there is a significant morbidity and mortality risk. Few recent reports suggest that allogeneic and autologous HCT may be feasible in patients who have recovered from COVID-19, but there is little data on the optimal timing and safety of HCT following the infection. High rates of COVID-19 community transmission were observed in a highly-vaccinated population of Singapore between September 2021 and April 2022, affecting many HCT recipients. In this study at the largest tertiary transplant centre in Singapore, we analyzed the outcome of patients who underwent HCT following COVID-19 infection in the preceding 120 days or with active COVID-19 infection during transplant. Methods We conducted a retrospective analysis of consecutive patients admitted to Singapore General Hospital for planned HCT from September 2021 and April 2022. Written informed consent was obtained, and patients were followed up for transplant-related outcomes. The date of diagnosis of COVID-19 was based on the first positive SARS-CoV-2 PCR nasopharyngeal swab. Patients who were diagnosed with COVID-19 within 120 days prior to stem cell infusion were included in the study. Results We studied 10 allogeneic and 1 autologous HCT patients, with acute myeloid leukaemia (n=3), acute lymphoblastic leukaemia (n=2), chronic myeloid leukaemia (n=2), myelofibrosis (n=1), severe aplastic anaemia (n=1), Hodgkin lymphoma (n=1) and multiple myeloma (n=1). Median interval between diagnosis of COVID-19 to HCT infusion was 53 days (range 1-118). 6 were tested negative by PCR and 2 were prolonged low-level viral shedders detectable by PCR, prior to HCT. 3 patients were diagnosed with COVID-19 immediately prior to HCT infusion, at Days -1, -3 and -5 respectively. Median duration of COVID-19 infection defined by time to negative PCR was 20 days. All allogeneic HCT patients had 2 doses of COVID-19 mRNA vaccines (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) prior to infection, and the autologous HCT patient was unvaccinated. Median receptor binding domain IgG serology titre (Abbott assay) in vaccinated patients was 1301 AU/ml at the time of COVID-19 diagnosis. COVID-19 disease severity by WHO guidelines was mild in 9, moderate in 1 and critical in 1 patient. 8 patients received antivirals; 5 of them had concurrent monoclonal antibodies (sotrovimab, n=4; casirivimab-imdevimab, n=1). Median age at HCT was 53 years (range 26-70); 64% of patients had low-risk HCT-comorbidity index, 45% were male, and 55% were of high-risk by the disease risk index. Allogeneic HCT patients received peripheral blood stem cells from matched siblings donors (MSD, n=3), matched unrelated donors (MUD, n=2) or haploidentical donors (n=5). 50% of patients received myeloablative conditioning regimen (n=5); and prophylaxis for graft-versus-host disease (GvHD) included calcineurin inhibitors and/or mycophenolate mofetil. Haploidentical transplant patients received post-transplant cyclophosphamide (PTCy, n=3) or ex-vivo TCRalpha-beta depleted grafts (n=2). A relapsed AML patient received haploidentical TCRalpha-beta depleted graft without conditioning regimen. A median of 5.5 x 10^6 CD34+ cells/kg (range 2.9-10.1) was infused. Median time to neutrophil and platelet engraftment were 10 days (range 10-17) and 12 days (range 10-20) respectively, in both MSD and MUD recipients (Table 1), comparable to that of non-COVID-19 cohorts. 2 patients died of non-relapse pulmonary complications on D+43 and D+50 post HCT respectively. 2 out of 10 allogeneic HCT patients developed grade II acute GvHD of skin, but none grade III-IV acute GvHD. Median follow up was 103 days (range 43-208), and GvHD-free/relapse-free survival (GRFS) among surviving patients at D+100 was 78%. There was no evidence of COVID-19 reinfection or late complications, or increase in viral reactivation of CMV, EBV and HHV6. Discussion Our study suggests that timely HCT can be safely performed with favourable outcome for patients with haematological malignancies, following acute COVID-19 infection in a fully-vaccinated cohort. Immunization, viral therapeutics and a careful disease risk-benefit assessment play a crucial role. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia

Recent studies have underscored the importance of gamma-delta (γδ) T cells in mediating potent MHC-unrestricted cytotoxicity in numerous malignancies. Here, we analyzed Vδ1 and Vδ2 γδ T cell subsets in newly diagnosed chronic myeloid leukemia (CML) patients (n = 40) who had initiated tyrosine kinase inhibitor (TKI) therapy including imatinib (n = 22), nilotinib (n = 14) and dasatinib (n = 4). Patient peripheral blood samples were analyzed at diagnosis and monitored prospectively at 3, 6, 12 and 18 months post-TKI. γδ T cells isolated from healthy donors and CML patients were used against K562, LAMA-84 and KYO-1 cell lines and against primary CML cells in cytotoxicity assays. We found large expansions of Vδ1 and Vδ2 T cells in patients at diagnosis compared to age-matched healthy donors (n = 40) (p < 0.0001). The γδ T cell reconstitution in patients on imatinib and also on nilotinib showed significant reductions of Vδ1 T cell and Vδ2 T cell absolute counts at 3 months compared to diagnosis. Importantly, Vδ1 and Vδ2 T absolute cell counts remained at normal levels from 3 months throughout the follow-up. Next, we observed susceptibility to specific lysis of primary CML tumor cells by Vδ1 T cells from healthy donors. Furthermore, we determined inherent cytotoxic reactivity by autologous patients’ Vδ1 T lymphocytes against primary CML tumor cells. Finally, the TCR clonality profiles showed in CML patients mostly polyclonal repertoires regardless of the TKI. Our results provide further evidence into γδ T cell antileukemia immunity in CML that might be beneficial for long-term disease control and treatment outcome.

An evaluation of the population characteristics, semen quality, and utilization status of autologous sperm cryopreservation and fertility preservation in for 662 patients: a 6-year monocentric retrospective study

BackgroundSperm cryopreservation is an effective method of fertility preservation for disease-related and social sperm freezing. In total, 662 subjects (range: 15–65 years-of-age; mean: 33.49 ± 8.79 years-of-age) were included in this study to investigate the population characteristics, semen quality, and usage of autologous sperm preservation patients in Beijing. Of these, 351 were cancer patients (53.02%, 31.14 ± 7.32 years-of-age) and 311 were non-cancer patients (46.98%, 36.14 ± 9.54 years-of-age).ResultsWe found that the number of preservation cases increased steadily from 2015 to 2019; 89.73% of these had a bachelor's degree or above; 54.83%, 41.54%, and 3.63% were single, married, and divorced, respectively. The cases of cancers and oligozoospermia accounted for 71.30% of all patients; therefore, most patients required fertility preservation due to disease. The cancer group had a significantly lower sperm concentration, rate of progressive sperm after the frozen-thawed test, total progressive motility sperm count after the frozen-thawed test, and recovery rate of progressive motile sperm (RRPM) than the non-cancer group (all P < 0.05). Sperm count-related parameters were significantly affected by testicular cancer, while sperm motility-related parameters and RRPM were significantly affected by leukemia. The utilization rate of preserved sperm was 6.34% after 6 to 78 months of follow-up. In terms of fresh or frozen embryo transfer, the clinical pregnancy rate was 56.76% or 50.00%, and the live birth rate was 24.32% or 21.43%, respectively.ConclusionThe need for autologous sperm preservation was dominated by patients with diseases, followed by the need for social sperm freezing. Tumors had a major negative impact on semen quality, and the usage rates of stored semen were at lower level compared to the number of sperm cryopreservation. Medical staff and patients should pay attention to both cognition-action consistency and cost-effectiveness in fertility preservation.

DNA Methylation Changes in Autologous Hematopoietic Stem Cell Transplant Patients.

Blood cancers may be potentially cured with hematopoietic stem cell transplantation (HCT); however, standard pre-assessments for transplant eligibility do not capture all contributing factors for transplant outcomes. Epigenetic biomarkers predict outcomes in various diseases. This pilot study aims to explore epigenetic changes (epigenetic age and differentially methylated genes) in patients before and after autologous HCT, that can serve as potential biomarkers to better predict HCT outcomes. This study used a prospective longitudinal study design to compare genome wide DNA methylation changes in 36 autologous HCT eligible patients recruited from the Cellular Immunotherapies and Transplant clinic at a designated National Cancer Center. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 850K BeadChip, showed a significant difference in DNA methylation patterns post-HCT compared to pre-HCT. Compared to baseline levels of DNA methylation pre-HCT, 3358 CpG sites were hypo-methylated and 3687 were hyper-methylated. Identified differentially methylated positions overlapped with genes involved in hematopoiesis, blood cancers, inflammation and immune responses. Enrichment analyses showed significant alterations in biological processes such as immune response and cell structure organization, however no significant pathways were noted. Though participants had an advanced epigenetic age compared to chronologic age before and after HCT, both epigenetic age and accelerated age decreased post-HCT. Epigenetic changes, both in epigenetic age and differentially methylated genes were observed in autologous HCT recipients, and should be explored as biomarkers to predict transplant outcomes after autologous HCT in larger, longitudinal studies.

Efficacy of Intramuscular Platelet Rich Plasma Versus Oral Antihistamine In Chronic Urticaria

Background: Chronic urticaria is defined as a pruritic skin disorder that persists daily or about daily for ˃6 weeks. Chronic urticaria is a common problem in Pakistan. The common treatment method is oral histamine. Currently the important treatment method used is autologous serum therapy. The objective of this study was to determine the efficacy of intramuscular platelet rich plasma versus oral antihistamine in the treatment of chronic urticaria Methodology: This study was randomized controlled clinical trial carried out at the Dermatology Department, Qazi Hussain Ahmad Complex Nowshera and alshifa clinic and skin aesthetic, Nowshera from May 2020 to May 2021. 100 patients were included in this research work. They were randomly divided into two groups of 50 patients each. One group was given autologous serum while the other was given antihistamine. The autologous serum group patients were treated by giving 9 intramuscular injection of autologous serum while the antihistamine group patients were treated with oral antihistamine on routine basis. UAS-7 (Urticaria Activity score-7) was used for measuring the effectiveness of both the treatment methods. Results: At baseline in autologous serum group, the Urticaria activity score was 36.1 (±6.7) while in antihistamine group it was 35.2 (±5.4) respectively. At baseline Urticaria activity score was non-significant (p=0.85). At 4th week the mean Urticaria activity score in autologous serum group and antihistamine group was 18.3(±3.6) and 30.2.1 (±5.1) (p=0.01). At 9th week in autologous serum group, the Urticaria activity score was 11.3 (±6.3) while in antihistamine group it was 22.6 (±4.9). (p=0.04) At 12th week the mean Urticaria activity score in autologous serum group and antihistamine group was 7.1(±5.4) and 20.4 (±7.3) respectively (p=0.01). Conclusion: Our study concludes that autologous serum therapy is more effective as compared to antihistamine in the treatment of chronic urticaria Keywords: Chronic Urticaria; Intramuscular platelet rich plasma; Oral antihistamine

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

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

ABCL-088 Subgroup Analysis in RE-MIND2: An Observational, Retrospective Cohort Study of Tafasitamab + Lenalidomide Versus Systemic Therapies in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Tafasitamab+lenalidomide (LEN), a chemo-free immunotherapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), demonstrated efficacy in autologous stem cell transplant-ineligible patients in the single-arm L-MIND study (NCT02399085). RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared patient outcomes from L-MIND with matched patient cohorts treated with other systemic therapies. Prolonged overall survival (OS) with tafasitamab+LEN was detected compared to a cohort of pooled systemic therapies (PST), bendamustine+rituximab (BR), rituximab+gemcitabine+oxaliplatin, polatuzumab vedotin+BR (pola-BR), and rituximab+LEN (R2). Comparable OS was detected versus CD19 chimeric antigen receptor T-cell therapies (CAR-T). However, limited information is available on the comparative effectiveness of tafasitamab+LEN in specific subpopulations. This study aimed to determine the relative effectiveness of tafasitamab+LEN versus other treatments for R/R DLBCL in clinically relevant patient subgroups in the absence of head-to-head trials. The L-MIND cohort was matched with RE-MIND2 patients using estimated propensity score-based 1:1 nearest neighbor matching balanced for a minimum of six covariates. Sensitivity analyses were conducted. The study was conducted at academic, public, and private hospitals in Europe, North America, and the Asia-Pacific region. Patients were ≥18 years old with histologically confirmed DLBCL and ≥2 prior systemic therapies for DLBCL, including ≥1 anti-CD20 therapy. Data are presented for tafasitamab+LEN versus PST, versus pola-BR, versus R2, and versus CAR-T. Hypothesis-generating analyses were conducted for patient subgroups of number of extranodal sites (ENS) (0-1 vs. ≥2) and elevated lactate dehydrogenase (LDH) (yes vs. no). The primary endpoint was OS. Of 3,454 patients enrolled, 961, 106, 106, and 149 were treated with PST, pola-BR, R2, and CAR-T, resulting in 76, 24, 33, and 37 matched pairs for patients receiving tafasitamab+LEN, respectively. Hazard ratios for OS for patients with ≥2 ENS were 0.803, 0.524, 0.478, and 1.459, and for patients with elevated LDH were 0.627, 0.585, 0.420, and 1.663, for comparisons of tafasitamab+LEN versus PST, pola-BR, R2, and CAR-T, respectively. There was a trend towards favoring tafasitamab+LEN in most patient subgroups. The combination may be associated with improved OS versus selected systemic therapies for certain patients with high-risk disease. These analyses are not powered for statistical comparison and should be interpreted with caution. Funding: MorphoSys AG.