Autologous Peripheral Stem Cell Transplantation Research Articles

Analysis of Factors Affecting Hematopoietic Stem Cell Mobilization Efficiency and Early Hematopoietic Reconstruction Indicators during Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

Purpose To analyze the factors affecting the mobilization efficiency of hematopoietic stem cells and hematopoietic reconstruction indicators during autologous peripheral hematopoietic stem cell transplantation. Methods The clinical data of 54 patients who underwent autologous peripheral blood hematopoietic stem cell mobilization and transplantation at Xuzhou Central Hospital from May 2016 to April 2023 were retrospectively analyzed. The gender, age, disease type, mobilization regimen, number of chemotherapy sessions, G-CSF (granulocyte colony-stimulating factor) dosage, and platelet number at the time of collection were also collected. Moreover, the relationship between these indicators with mobilization results and hematopoietic reconstruction was analyzed. Results Results showed that age, disease type, and number of collections were significantly related to the mobilization results (number of CD34+ hematopoietic stem cells). Furthermore, multivariate analysis showed that the number of collections was an independent factor affecting mobilization efficiency. Similarly, age, platelet value at the time of collection, CD34+ stem cell value during collection, white blood cell count, and number of chemotherapy times were significantly related to the time of megakaryocytic hematopoietic reconstruction. Multifactor analysis found that age and platelet count were independent factors affecting the reconstruction time of the megakaryocytic system. However, no factor was related to the time of granulocyte hematopoietic reconstruction. Conclusion Platelet count and age when collecting hematopoietic stem cells are closely related to megakaryocytic hematopoietic reconstruction and are key indicators of early hematopoietic reconstruction after autologous hematopoietic stem cell transplantation.

Brentuximab vedotin therapy followed by autologous peripheral stem cell transplantation as a viable treatment option for an older adult with transformed lymphoma: a case report and literature review.

This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.

Does early granulocyte colony-stimulating factor administration in autologous peripheral blood stem cell transplantation shorten the duration of hospitalization in patients with multiple myeloma?

Aims: Autologous peripheral blood stem cell transplantation (PBSCT), performed with high-dose melphalan support following induction therapy is still the gold standard method of treatment for multipl myeloma (MM)patients suitable for transplantation. It was aimed, with this retrospective study, to investigate the effects of early (1 day after PBSCT) and late (5 days after PBSCT) initiation of granulocyte colony-stimulating factor (G-CSF) support following PBSCT on engraftment time, febrile neutropenia, and length of hospital stay (LOS) in MM patients. Methods: This study included 70 patients with MM, who underwent PBSCT in Erciyes University. Two groups were administered 5µg/kg filgrastim, subcutaneously, either 1 day or 5 days after PBSCT, until neutrophil engraftment was reached. Results: Both neutrophil and platelet engraftment occurred in significantly shorter times in the early G-CSF group compared to late G-CSF group; the median times to neutrophil engraftment were 10 (8-13) and 11 (7-15) days, respectively, and the median times to platelet engraftment were 11 (10- 16) and 13 (11- 21) days (p=0.001). Also, the median LOS was also significantly shorter in the early G-CSF group compared to late G-CSF group; 14 (10-22) vs 16 (11- 33) days, respectively (p=0.016). No significant difference was found between the groups in terms of frequency of febrile neutropenia. Conclusion: The initiation of G-CSF support early, following PBSCT in MM patients, accelerated neutrophil and platelet engraftment and shortened the LOS as compared to the initiation of G-CSF support late, with no significant difference in the frequency of febrile neutropenia.

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34+ hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

Peripheral blood stem cell harvesting in young children weighing less than 15 kg

Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in the pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6–5.6) years and a body weight of 11.0 (range, 6.6–14.7) kg. The median CD34+ cells in each apheresate were 4.2 (range, 0.01–40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The preapheresis hematopoietic progenitor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the preapheresis HPC count ≥20/μL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (area under the curve 0.787).

Optimizing Autologous Stem Cell Transplantation in Multiple Myeloma: The Impact of Intensive Chemomobilization

Most transplant-eligible multiple myeloma (MM) patients undergo autologous peripheral blood stem cell collection (PBSC) using G-CSF with on-demand plerixafor (G ± P). Chemomobilization (CM) can be used as a salvage regimen after G ± P failure or for debulking residual tumor burden ahead of autologous peripheral blood stem cell transplantation (ASCT). Prior studies utilizing cyclophosphamide-based CM have not shown long-term benefits. At our center, intensive CM (ICM) using a PACE- or HyperCVAD-based regimen has been used to mitigate "excessive" residual disease based on plasma cell (PC) burden or MM-related biomarkers. Given the lack of efficacy of non-ICM, we sought to determine the impact of ICM on event-free survival (EFS), defined as death, progressive disease, or unplanned treatment escalation. We performed a retrospective study of newly diagnosed MM patients who collected autologous PBSCs with the intent to proceed immediately to ASCT at our center between 7/2020 and 2/2023. Patients were excluded if they underwent a tandem autologous or sequential autologous-allogeneic transplant, had primary PC leukemia, received non-ICM treatment (i.e., cyclophosphamide and/or etoposide), or had previously failed G ± P mobilization. To appropriately evaluate the impact of ICM among those who potentially could have received it, we utilized a propensity score matching (PSM) approach whereby ICM patients were compared to a cohort of non-CM patients matched on pre-ASCT factors most strongly associated with the receipt of ICM. Of 451 patients identified, 61 (13.5%) received ICM (PACE-based, n = 45; hyper-CVAD-based, n = 16). Post-ICM/pre-ASCT, 11 patients (18%) required admission for neutropenic fever and/or infection. Among 51 evaluable patients, the overall response rate was 31%; however, 46 of 55 evaluable patients (84%) saw a reduction in M-spike and/or involved free light chains. Among those evaluated with longitudinal peripheral blood flow cytometry (n = 8), 5 patients (63%) cleared circulating blood PCs post-ICM. Compared to patients mobilized with non-CM, ICM patients collected a slightly greater median number of CD34+ cells (10.8 versus 10.2 × 10⁶/kg, P = .018). The median follow-up was 30.6 months post-ASCT. In a PSM multivariable analysis, ICM was associated with significantly improved EFS (hazard ratio [HR] 0.30, 95% CI 0.14 to 0.67, P = .003), but not improved OS (HR 0.38, 95% CI 0.10 to 1.44, P = .2). ICM was associated with longer post-ASCT inpatient duration (+4.1 days, 95% CI, 2.4 to 5.8, P < .001), more febrile days (+0.96 days, 95% CI 0.50 to 1.4, P < .001), impaired platelet engraftment (HR 0.23, 95% CI 0.06 to 0.87, P = .031), more bacteremia (OR 3.41, 95% CI 1.20 to 9.31, P = .018), and increased antibiotic usage (cefepime: +2.3 doses, 95% CI 0.39 to 4.1, P = .018; vancomycin: +1.0 doses, 95% CI 0.23 to 1.8, P = .012). ICM was independently associated with improved EFS in a matched analysis involving MM patients with excessive disease burden at pre-ASCT workup. This benefit came at the cost of longer inpatient duration, more febrile days, greater incidence of bacteremia, and increased antibiotic usage in the immediate post-ASCT setting. Our findings suggest that ICM could be considered for a subset of MM patients, but its use must be weighed carefully against additional toxicity.

Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma.

Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available. We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients. CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5) mutations. Presence of CH in the PBSC product was an independent predictor of t-MN (adjusted hazard ratio [aHR], 4.50 [95% CI, 1.54 to 13.19]). Notably all patients with TP53 mutations in the PBSC product developed t-MN, whereas none of the patients with DNMT3A mutations alone (without co-occurring TP53 or PPM1D mutations) did. Presence of TP53 and/or PPM1D mutations was associated with a 7.29-fold higher hazard of t-MN when compared with individuals carrying no CH mutations (95% CI, 1.72 to 30.94). The presence of TP53 and/or PPM1D mutations was also associated with a 4.17-fold higher hazard of nonrelapse mortality (95% CI, 1.25 to 13.87). There was no association between CH and relapse-related mortality. The presence of TP53 and/or PPM1D mutations in the PBSC product increases the risk of post-aPBSCT t-MN and nonrelapse mortality among patients with HL and may support alternative therapeutic strategies.

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI,0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Challenges and Outcomes of the First Stem Cell Transplant Program in Tanzania, East Africa.

Due to the significant resources involved in creating HSCT programs there is a significant disparity in the availability of this treatment modality between the developed and developing countries. This manuscript details the process and the outcomes of the first HSCT program in East Africa which was started at Muhimbili National Hospital (MNH) in Dar-es-Salaam, Tanzania. Information and data were collected on the processes which had been implemented for starting the HSCT program at MNH. The details of the collaborations, training, infrastructure development, and acquisition of the biomedical equipment, as well as the actual process for HSCT, as well as the outcomes of treatment are described. Observations. The project has been detailed in 4 stages for ease of description: Stage 1: Preparatory work which was performed by the Government of Tanzania, as well as the administrators and clinicians from MNH (July 2017-September 2021). Stage 2: Exploratory gap analysis by the teams from MNH and International Haematology Consortium of HCG Hospital, India (HCG-IHC) in October 2021. Stage 3: Activities for closure of gaps (November 2021). Stage 4: Stem Cell Transplantation Camps (November 2021 to March 2022). 11 peripheral blood stem cell transplants were done in two camps, November 2021 (5 patients), and February 2022 (6 patients). 10 patients underwent autologous peripheral blood stem cell transplantation for multiple myeloma and 1 for lymphoma. The median duration of hospital stay was 19 ± 6 days. The median time for neutrophil engraftment, it was on 8.8 ± 0.8 days, and for platelet engraftment was 9.6 ± 2.4 days. Progression-free survival was 100%, and there was no mortality. Commonalities in the socioeconomic challenges in developing countries can be leveraged to create robust HSCT programs in other developing countries.

Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system.

Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Age, creatinine, neutrophil-to-lymphocyte ratio, and Child-Turcotte-Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633-0.738) and better clinical utility compared with other conventional prognostic models. The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals.

Day 100 Natural Killer Cell/CD14+HLA-DRDIM ratio and survival in lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

The infusion of autograft Natural Killer Cells (NKC)/CD14+ HLA-DRDIM ratio is a predictor of survival in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). This study evaluated if the Day 100 NKC/CD14+ HLA-DRDIM ratio still functions as a prognostic immune-biomarker. This was a retrospective, single-institution, cohort analysis including 107 patients in this study that had clinical assessment at Day 100 post-APBHSCT from our prior phase III trial. We evaluated the prognostic ability of the Day 100 NKC/CD14+ HLA-DRDIM ratio to predict overall survival (OS) and progression-free survival (PFS) using Cox regression model for outcome analysis and survival by Kaplan-Meier method. The median follow-up from day 100 was 94.7 months (range 4.83-158.1 months) for the entire cohort. Patients with a Day 100 NKC/CD14+ HLA-DRDIM ratio ≥1.67 experienced better OS and PFS versus those with a Day 100 NKC/CD14+ HLA-DRDIM ratio <1.67: median OS was not reached versus 49.7 months, the 5-year OS rates were 91% (95% CI, 81%-96%) versus 40% (95% CI, 27%-55%), p<.0001, respectively; and median PFS was not reached versus 23.5 months, the 5-year PFS rates were 66% (95% CI, 55%-81%) versus 21% (95% CI, 15%-40%), p<.0001, respectively. Day 100 NKC/CD14+ HLA-DRDIM ratio was an independent predictor for OS and PFS in the multivariate analysis. Day 100 NKC/CD14+ HLA-DRDIM ratio is a prognostic immune-biomarker in lymphoma patients post- APBHSCT.

Primary Ewing’s sarcoma of the kidney: description of two rare clinical cases and review of world literature

Ewing’s sarcoma (ES) of the kidney is an extremely rare malignant tumor characterized by an aggressive course, and therefore the disease has an unfavorable prognosis. Due to the rare occurrence, standards for the treatment of ES of the kidney have not been developed; an integrated approach is often used in therapy. In this article, we present a description of two clinical cases of kidney damage with ES in patients aged 10 and 16 who were treated at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. In the first case, there was a metastatic lesion of the kidney with the localization of the primary focus in the pelvic bones, in the second, primary ES of the kidney was diagnosed. Both patients had stage IVb at the time of diagnosis (TNM classification American Joint Commission on Cancer). In both patients, after induction chemotherapy, a complete therapeutic response (complete therapeutic pathomorphosis) was obtained. In an integrated approach, in addition to standard chemotherapy, surgery and radiation therapy, in both cases, high-dose chemotherapy with autologous peripheral stem cell transplantation was used, which made it possible to create favorable conditions for long-term remission in one of the patients, even despite the initial prevalence of the process.

Scalp Cooling to Prevent Hair Loss in Multiple Myeloma Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation

The best outcomes for multiple myeloma progression-free and overall survival include the use of high-dose melphalan and autologous peripheral blood stem cell transplantation. Melphalan is given at a dose of 140 - 200 mg/m2 as a single dose two days before or in divided daily doses immediately prior to the reinfusion of stem cells. Melphalan causes nearly complete hair loss in all patients at these doses, (CTCAE v5 Grade 2). Hair typically falls out after 10-15 days and doesn't begin to grow back for 10-12 weeks. This outcome is widely expected and leads some patients to avoid doing an otherwise life sustaining procedure. In those that do proceed with the transplant, the alopecia can be emotionally harmful. Cryotherapy is commonly used to reduce melphalan side effects in the GI tract. Melphalan typically will cause diarrhea, nausea, and mouth sores yet a randomized trial done in 2006 showed that swallowing ice chips for 6 hours starting 30 minutes before the melphalan is given can reduce these unpleasant and potentially dangerous side effects by 60% (Lilleby et. al. 2006). We at Cedars-Sinai routinely have patients do oral cryotherapy for 3.5 hours starting 30 minutes prior to each dose of melphalan. This has reduced patient side effects substantially in our experience and is considered our standard of care. Chemotherapy drugs, such as melphalan, typically injure bone marrow, intestinal lining and other cells with high metabolism and rapid cell division. Hair follicles also have these properties and is likely why many chemotherapeutics cause hair loss when used. Scalp cooling has been used to prevent hair loss in many patients undergoing chemotherapy for solid tumors. For some women with breast cancer, this hair loss was reported to be more traumatizing than losing a breast to mastectomy (Zhang et. al. 2022). The use of cold caps during chemotherapy exposure time has helped reduce hair loss, presumably by causing vasoconstriction and reducing distribution of the drug to the hair follicle. This intervention has been effective even when drugs which have longer durations of circulation have been given. While there is a theoretical risk that scalp cooling may impair the killing of malignant cells in the scalp by the chemotherapy, there is no evidence of a heightened risk in studies. The penetration of the cold should not reach the skull bone where myeloma cells may reside and is generally to a depth of only a few millimeters. The toxicity of scalp cooling is minimal. In a study of 27 participants using scalp cooling for solid tumors, 96% reported that the procedure was worth the time, effort, cost, and discomfort and would recommend usage to others undergoing the same chemotherapy treatment (Sitarz et. al. 2022). While scalp cooling has been used to prevent hair loss in patients undergoing chemotherapy for solid tumors, no reports were found for its usage for multiple myeloma or other hematologic malignancies. Since melphalan has a much shorter half-life, (70 minutes), than most other chemotherapy drugs used for solid tumors, it is anticipated that scalp cooling will be more efficacious when used with this drug. In fact, after 5 hours the concentration of melphalan should only be 5% of that present immediately after administration. A 57-year-old patient with multiple myeloma undergoing high-dose chemotherapy with melphalan 200 mg/m2 opted to use the commercially available Penguin Cold Cap to prevent losing her hair. The device was started 60 minutes before and continued for 5 hours after the melphalan infusion was started at Day -2 and Day -1 prior to her autologous stem cell transplant. The procedure was well tolerated, and the patient had no signs of any hair loss after the stem cell transplant. Based upon this experience, a study was initiated to further assess the efficacy of scalp cooling with the Penguin Cold Cap device in multiple myeloma patients receiving autologous stem cell transplants. An update with results of this study will be presented at the meeting. A positive outcome may improve the percentage of people willing to undergo this life-sustaining procedure and improve the quality of life of those who do it.

Salvage Autologous Peripheral Blood Stem Cell Transplantation after the Development of tMDS or AML in Multiple Myeloma Patients

Multiple Myeloma (MM) patients are often treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) for disease control. Lenalidomide is typically used as maintenance but results in an estimated 3.3% chance of developing a therapy-related myeloid neoplasm (TMN) typically myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). This complication is often devastating with a median survival for those with a TMN of just 13 months. Over the past 6 years, 4 patients with multiple myeloma who developed a TMN were treated with a salvage ASCT using banked stem cells collected prior to their initial ASCT and before lenalidomide maintenance. None of these patients qualified for an allogeneic transplant. Melphalan 140 - 200 mg/m2 was used as conditioning prior to infusion of the peripheral blood stem cells, resulting in successful MDS/AML disease control. Case 1 = 61-year-old man with MM initially treated with CyBorD then transplanted in 2010. Post transplant treatment included lenalidomide maintenance, followed by a variety of salvage regimens over the next 7 years including thalidomide, carfilzomib, daratumumab and pomalidomide. He developed cytopenias evaluated by bone marrow biopsy in May 2017. This showed tMDS (Karyotype 47-48, XY, der (5)t(5:20)(q11.1;q11.1), +19, der(21:22)(q10:q10),+2~3mar[cp11]/46-48,idem,-der(5),+20[cp5]/46,XY[4]. FISH confirmed deletion 5q in 76% and loss of chromosome 5 in 6.5% of cells. NGS showed a frame shift mutation of TP53 at a variant allele frequency of 92.5%. He underwent a second ASCT in Aug 2017 and recovered normal hematopoiesis within three weeks. Unfortunately, he developed an aggressive relapse of his multiple myeloma 9 months later and succumbed from refractory multiple myeloma 14 months after the salvage transplant, without evidence of MDS. Case 2 = 72-year-old man with MM initially treated with CyBorD then an ASCT in May 2015. Lenalidomide maintenance was continued until October 2017 when he developed severe thrombocytopenia and circulating blasts. A bone marrow biopsy showed tMDS EB-1. Cytogenetics 46, XY t(3:21) (q26.2,q22) [18]/46, XY[2]. He received a second ASCT after melphalan 140 mg/m2 in Oct 2017 followed by recovery of normal blood counts. Bone marrow biopsy showed complete remission. He remains in remission from both the multiple myeloma and MDS almost 6 years later without any further therapy. Case 3 = 65-year-old man with MM treated with bortezomib + dexamethasone followed by ASCT in Aug 2012. He received maintenance lenalidomide for 4 years but then progressed. In Jan 2018 he developed pancytopenia and bone marrow biopsy demonstrated MDS with ringed sideroblasts. Cytogenetics were normal but NGS showed mutations of ASXL1, RUNX1, SF3B1, SETBP1 and DNMT3A. He underwent a second ASCT using his banked stem cells after melphalan 140 mg/m2 in Jan 2018 followed by full hematopoietic recovery. A repeat bone marrow biopsy in March 2022 showed persistent MDS harboring ASXL1, SF3B1, and DNMT3A mutations, but no detectable RUNX1 or SETBP1 abnormalities. His multiple myeloma remains in remission &amp;gt;5 years later. He receives only intermittent erythropoietin to maintain a Hgb of 11. Case 4 = 58-year-old man with MM initially treated with CyBorD followed by an ASCT in May 2014. He received lenalidomide maintenance but relapsed multiple times after 4 years ultimately complicated by renal failure requiring permanent dialysis. In March 2022 he developed pancytopenia. Bone marrow biopsy showed 15% blasts harboring del(5q), del(17p) and trisomy 8 by FISH. NGS demonstrated a mutation of ASXL1, and a copy number loss of TP53. Six months of decitabine did not improve his blood counts. In Dec 2022 he underwent a second ASCT after melphalan 140 mg/m2. A repeat bone marrow biopsy in Feb 2023 showed a complete morphological remission with a normal NGS. He is off all treatment 8 months post-transplant other than erythropoeitic support due to ongoing dialysis-dependent renal failure. The development of TMN is an uncommon but devastating event in patients with multiple myeloma after ASCT and lenalidomide maintenance. These patients responded well to a salvage ASCT using banked stem cells. This approach was well tolerated and provided durable hematopoietic recovery. Second ASCT using banked autologous stem cells should be considered in such patients who are not otherwise candidates for allogeneic transplantation.

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (&amp;gt;38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

The Combination of Pegfilgrastim and Filgrastim Improves the Outcomes of Mobilization and Engraftment after Transplantation of Autologous Hematopoietic Stem Cells for the Treatment of Lymphoma

BACKGROUND : Hematopoietic stem cell transplantation (HSCT) is broadly utilized for the treatment of lymphoma. Autologous peripheral blood stem cell (PBSC) transplantation (ASCT) requires mobilization of hematopoietic stem cell/ hematopoietic progenitor cell (HSC/HPC) in peripheral blood (PB) to collect HSCs. The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF, recombinant human granulocyte colony-stimulating factor) in ASCT is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: To test the hypothesis that the combination of pegfilgrastim and filgrastim schedule has superiority, we retrospectively investigated a cohort of 107 lymphoma patients who received auto-HSCT and collection in the First Hospital of Jilin University from Jan 1st 2015 to Dec 1st 2022. These patients were categorized into PEG+FIL group and FIL group. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number PBSCs. Demographic information, laboratory results, and treatment plans were collected for these two groups of patients. RESULTS：We compared their mobilization efficacy (mononuclear cell [MNC] and CD34 + cell counts) and transplantation efficacy (days to leukocyte and platelet recovery post-transplantation). Successful ASCT mobilization was achieved in 93 patients (86.9%), with the PEG+FIL group exhibiting a higher success rate compared to the FIL group (89.2% [58/65] vs. 83.3% [35/42], p = 0.032). The PEG+FIL group also demonstrated significantly higher CD34+ cell counts [MNC: 8.9 (6.9, 11.2) vs. 7.8 (6.2, 9.8) × 10 8 cells/kg, p = 0.024; CD34 + cell count: 7.5 (5.6, 13.0) vs. 4.9 (3.2, 9.2) × 10 6 cells/kg, p = 0.008] and a lower incidence of neutropenic fever compared to the FIL group (11.8% vs. 24.3%, p = 0.038). The PEG+FIL group also demonstrated a shorter mean leukocyte recovery time in autologous stem cell transplantation than the FIL group (10.02 ± 0.73 vs. 10.9 ± 1.1 days, p &amp;lt; 0.001). To delve deeper into the safety considerations of both groups, we evaluated the advantages of each regimen and the methodologies for selecting time windows. A bone marrow aspiration and biopsy were performed on all patients before stem cell collection. Among 18 patients who had a hematopoietic area less than 30% and a fat area greater than 40%, 10 were in the PEG+FIL group and 8 in the FIL group. For patients who required only one collection, the durability was 80% in the PEG+FIL group compared to 0% in the FIL group (p &amp;lt; 0.01), indicating a superior recommendation for patients with a bone marrow hematopoietic area of less than 30%. In the PEG+FIL group, monitoring was carried out for PB CD34 + percentage and WBC count following pegfilgrastim administration, with subsequent computation of CD34 + cells in PB. Filgrastim administration was found to be optimal 5-6 days post-pegfilgrastim administration. CONCLUSIONS: In conclusion, relative to conventional filgrastim mobilization, the conjunctive use of pegfilgrastim and filgrastim demonstrates superior efficacy, non-inferior safety during ASCT. The schedule enhanced the the outcomes of mobilization in the patients of less hematopoietic area. KEY WORDS: Pegylated recombinant human granulocyte-stimulating factor (pegfilgrastim, PEG-rhG-CSF), recombinant human granulocyte-colony stimulating factor (filgrastim, rhG-CSF), lymphoma, hematopoietic stem cell transplantation (HSCT) autologous hematopoietic stem cell mobilization.

Day 100 Inhibitory KIR2DL2 and Activating NKp30 Natural Killer Cell Receptors Predicts Survival Post-Autologous Stem Cell Transplantation in Lymphomas

Introduction: Our group previously published that the infusion autograft inhibitor KIR2DL2 (CD158b+CD337-) and activating NKp30 (CD158b- CD337+) Natural killer (NK) cells receptors were predictors of clinical outcomes in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) (Porrata et al. Leukemia Research 2019; 81: 1-9). To assess if these subsets of NK cells still hold clinical relevance, we set up to investigate their prognostic ability to predict clinical outcomes at Day 100 post-APBHSCT. Methods: 107 lymphoma patients who participated in our double-blind phase III trail (Porrata et al, Biology of Blood and Marrow Transplantation 2016; 22(6); 1017-1023) and had clinical assessment at Day 100 post-APBHSCT were included in this study. Nkp30 and KIR2DL2 at Day 100 were assessed by flow cytometry analysis. Results: With a median follow-up for the entire cohort from Day 100 was 94.7 months (range: 4.83-158.1 months). Figure 1 shows the overall survival (OS) and progression-free survival (PFS) based on the absolute numbers of KIR2DL2 and Nkp30 NK cells. At Day 100, patients with a KIR2DL2 &amp;lt; 0.08 and Nkp30 ≥0.19 experienced superior OS and PFS compared with patients with a Day 100 KIR2DLD2 ≥0.08 and NKp30 &amp;lt; 0.19. In the multivariate analysis both the KIR2DL2 [OS: HR = 1.767, 95%CI, 1.302-30.31, p &amp;lt; 0.04; and PFS: HR = 2.663, 95%CI, 1.108-6.403, p &amp;lt; 0.03] and Nkp30 [OS: HR = 2.594, 95% CI, 1.239-5.432, p &amp;lt; 0.01; and PFS: HR = 3.676, 95% CI, 1.875-7.206, p &amp;lt; 0.01] were independent predictors for OS and PFS. Conclusion: Day 100 inhibitory KIR2DL2 and activating NKp30 NK cells are prognostic immune-biomarkers in lymphoma patients undergoing APBHSCT.

Reverse Autologous Peripheral Blood Stem Cell Transplantation after Allogeneic Transplantation to Restore Immune Function and Pancytopenia

Despite advances in multiple myeloma treatment the disease remains challenging to treat with repeated relapses in most. For high-risk younger patients, allogeneic transplants are occasionally performed. While curative in some, complications can include the development of opportunistic infections and secondary malignancies. Furthermore, patients relapsing after an allogeneic transplant may have poor bone marrow reserve limiting the ability to use subsequent therapies. We describe two patients who underwent a “reverse” autologous peripheral blood stem cell rescue using stem cells banked prior to allogeneic transplantation. The outcomes were successful and led to full engraftment and correction of their immunodeficiencies and pancytopenia respectively. Case 1: A 37-year-old woman was diagnosed with multiple myeloma during routine testing for an in-vitro fertilization assessment. She had ISS stage 2 disease and was treated with CyBorD, followed by an autologous stem cell transplantation. Lenalidomide plus dexamethasone was used as maintenance. She relapsed after just one year then progressed through single agent carfilzomib and then bendamustine. After responding to 2 cycles of DCEP she had a 10/10 matched unrelated donor CD34-selected allogeneic transplant. The patient was EBV positive, but the donor was not. Four months post-transplant she developed tonsillar PTLD with a rising EBV DNA titer and was treated with rituximab. Her CD4 count was 46. Her multiple myeloma relapsed thereafter necessitating treatment with daratumumab. She then developed rituximab-resistant monomorphic PTLD which then responded to brentuximab-vedotin and donor lymphocyte infusions. The multiple myeloma relapsed again and was treated with daratumumab + pomalidomide + dexamethasone. After a rising EBV DNA titer, brentuximab-vedotin was restarted but the lymphoma progressed again with a 5 x 3 cm anterior mediastinal mass biopsy proven to be monomorphic PTLD. R-CHOP was given for 4 cycles but resulted in only a partial response. Due to subsequent rapidly symptomatic and progressive disease a decision was made to use high-dose melphalan (200 mg/m2) followed by a reinfusion of her previously collected autologous stem cells to restore her T-cell immunity and hopefully control her lymphoma. She engrafted uneventfully at Day + 12 with chimerism studies showing autologous hematopoiesis and a CD4 count of 856. Her post-transplant course was complicated by renal thrombotic microangiopathy treated successfully with eculizumab. After further myeloma relapses, she is currently alive and well and in remission while on teclistamab over 4 yrs after her 2 nd autologous PBSC transplant. Her lymphoma has resolved. Case 2: A 37-year-old-male with beta-thalassemia was noted to have an elevated total protein on routine blood testing for a life insurance policy. Work up revealed multiple myeloma with a t(4:14) abnormality and complex cytogenetics. After initial observation he was started on KRD for progressive anemia. A VGPR was obtained and consolidated with an autologous PBSC transplant. He was maintained on Ixazomib+lenalidomide+dexamethasone but relapsed 2 years later with a sacral mass. After progressions though daratumumab+pomalidomide+dexamethasone then carfilzomib and then XRT to a large chest mass followed by DCEP as salvage, he underwent a 9/10 mismatched allogeneic transplant. He developed Grade 2 skin GVH but had disease progression again after just 6 months. Salvage treatment with elotuzumab+pomalidomide+dexamethasone then DCEP and subsequently ciltacabtagene autoleucel were unsuccessful with progression after just 6 weeks from the latter. He was treated again with DCEP but became transfusion dependent after the 2 nd cycle and had progressive disease again. Due to symptomatic myeloma and pancytopenia he underwent a reverse autologous PBSC transplant using banked stem cells. He engrafted uneventfully on Day +11 and despite recurrent multiple myeloma, he is currently in remission while on talquetamab. His beta-thalassemia returned. These cases demonstrate the ability to reverse an allogeneic transplant successfully using previously stored autologous peripheral blood stem cells. The recovery allowed for resumption of effective anti-cancer treatment that became lifesaving. Whether this approach could correct patients with unrelenting GVH issues should be contemplated as well.

A Case Report of Peripheral Neuropathy after Induction Chemotherapy before Autologous Peripheral Blood Stem Cell Transplantation in a Patient with Multiple Myeloma with Amyloidosis Treated with Complex Korean Medicine Treatment

Introduction: We present a case of multiple myeloma with amyloidosis, which has features of peripheral neuropathy after induction chemotherapy before autologous peripheral blood stem cell transplantation, in a 56-year-old woman with Korean medicine.Case Presentation: For 17 days of hospitalization, the patient with complaints of numbness and a tingling sensation in the hands and feet was treated with acupuncture, herbal medicine. To reduce the symptoms, we provided Korean medicine treatments, including herbal medicine, acupuncture, and moxibustion. The Visual Analog Scale (VAS) was used to evaluate the results of the treatment. Until discharge, the VAS scores decreased for both hands and the foot tingling sensation.Conclusion: According to these results, Korean medicine treatment may be considered an effective treatment for tingling sensations in a patient with multiple myeloma with amyloidosis. Prospective studies are needed in the future to confirm and expand these findings.