Autologous Bone Marrow Transplantation Research Articles

Outcome of autologous bone marrow transplant in patients with relapsed and refractory diffuse large B-cell lymphoma in relation with prognostic factor: A single-center experience

Abstract: BACKGROUND Currently, about 50% of diffuse large B-cell lymphoma patients are relapsed following their complete response to first-line therapy. The treatment strategy for fit patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) has been done with salvage therapy with non-cross resistant combination chemo-immunotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). OBJECTIVES: The aim of study was to evaluate the outcome of ASCT for R/R DLBCL in relation to certain prognostic parameters. PATIENTS, MATERIALS AND METHODS: This is retrospective study, conducted from May 2014 to December 2022, at Hematology and BMT Center of Medical City Complex in Baghdad. Thirty-six patients with R/R DLBCL were investigated pre- and post-ASCT; the recorded data included patient disease status pre-transplant, early mortality rate, and type of response at day 100 post-transplant and, survival rate, relapsed rate, and mortality at the end of the study were documented accordingly. RESULTS: The mean age of DLBCL patients in this study was 41.3 (14–65) years, post-ASCT at day 100; there were 33 (91.6%), 2 (5.5%), and 1 (2.7%) patients in complete remission, relapsed progressive disease, and death, respectively, At 3-year posttransplant, the overall survival (OS) was 71%, whereas the event-free survival (EFS) was 59%. According to disease status pre-ASCT, the OS was 62%, 80%, and 66% with P = 0.7, whereas the EFS was 66%, 60%, and 50% with P = 0.5 for CR, UCR, and PR, respectively. CONCLUSION: Iraqi bone marrow transplant center data showed acceptable OS and EFS results in the treatment of R/R DLBCL patients in areas where there is no more option in terms of better OS and EFS but with insignificant relation to the available prognostic factor.

Development of Bone Marrow Transplantation Strategies

The use of alternative stem cell sources, the growth of supportive healthcare facilities, and the expansion of indications for bone marrow transplantation (BMT) as well as partially matched donors from the same family are all continuing evolutionary trends as the use of BMT has been developed and expanded to include donors who are not related by blood but have Partial histocompatibility antigen compatibility. Although the outcomes of these transplants are not as good as those performed with first-degree siblings, patients with leukemia, aplastic anemia, and immunodeficiency disorders who cannot receive treatment otherwise they can receive it now. Patients suffering from diseases such as acute myeloid leukemia, acute lymphoblastic leukemia, and Hodgkin lymphoma also show success with autologous bone marrow transplants. Furthermore, bone marrow or blood stem cell support is used after intensive chemotherapy. Patients with stage II, III, and IV breast cancer can benefit from treatment with bone marrow cells found in peripheral blood. In this review, the most important developments in autologous and allogeneic bone marrow transplantation, the control of infectious diseases, and the use of gene therapy to alter genetic disorders that are transmitted from parents to their offspring through bone marrow or peripheral blood infusions are outlined.

Mantle cell lymphoma with skin involvement: Case report of a rare manifestation in a patient with initial diagnosis of chronic lymphocytic leukemia

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin's lymphoma, which mainly affects males. It has a variable clinical presentation, with a course ranging from indolent cases that do not require treatment for years to very aggressive cases. Skin involvement is a rare event. Although most patients have disease in stage III or IV at diagnosis, they generally present with good functional status. In immunohistochemistry, CD5 is commonly expressed, a feature it shares with chronic lymphocytic leukemia. Cyclin D1 and SOX11 expression are present in almost all cases. Treatment depends on multiple factors such as age, frailty, comorbidities, disease stage, symptoms and morphological characteristics. We present the case of a male patient initially diagnosed with chronic lymphocytic leukemia who was started on treatment with ibrutinib. A biopsy of the right earlobe was subsequently performed, which documented secondary skin involvement due to a classic histological variant of mantle cell lymphoma. The patient was treated with chemotherapy between March and July 2022, with positron emission tomography at the end of the proposed cycles with complete metabolic response, so maintenance treatment with rituximab was performed and subsequently consolidated with an autologous bone marrow transplant. To date, the patient is in remission of the disease.

Pattern of Immune Reconstitution Post Allogeneic Stem Cell Transplant: Data From a Resource Constraint Country.

To determine the Pattern of immune reconstitution (IR) post allogeneic stem cell transplant at six months. Prospective observational study. Place and duration of the study: This study was conducted at The Armed Forces Bone Marrow Transplant Centre (AFMBTC) Rawalpindi, Pakistan, from May 2022 to December 2022. After approval from the institutional review board, informed/written consents were taken from patients. All patients (both genders, irrespective of age) undergoing allogeneic hematopoietic stem cell transplant were included in the study. Patients undergoing haplo-identical or autologous bone marrow transplants were excluded from the study. Innate immune reconstitution was checked by complete blood count and adaptive immune reconstitution at six months was checked lymphocyte subset analysis and serum immunoglobulin levels. Data was entered in pre-designed proforma and was analyzed using IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. This study analyzes 43 patients, including 67% (n=29) males. The median age at the time of HSCT was 11.19 years. Cellular and humoral reconstitution at six months after transplant was used to assess immune reconstitution. Innate immune reconstitution was checked by complete blood count for count recovery (Neutrophil engraftment), and adaptive immune reconstitution (cellular/humoral) at six months was checked lymphocyte subset analysis and serum immunoglobulin levels. By using chi-square, significant associations were found as pre-transplant condition regimen with CD4 (PChi= 0.001), GVHD prophylaxis with CD4 (PChi= 0.04), source of stem cells with CD19 (PChi= 0.008), patient-donor gender disparity with CD19 (PChi= 0.05), GVHD treatment low CD19 (PChi= 0.04), patient-donor relationship with IgA(PChi= 0.007), IgG (PChi= 0.001), and IgM (PChi= 0.001), gender of the patient with IgA (PChi= 0.04). Our data suggested thatat post-transplant six months, there was adequate immune reconstitution except for CD4 and CD4:CD8 ratio. Therefore, post-transplant, six months in Allo-HSCT could be considered for immunization.

Impact of early palliative care intervention in autologous bone marrow transplantation: feasibility of a multicentric study

IntroductionThis prospective multicentre study evaluates the impact of Palliative Care Unit (PCU) intervention (Experimental Group, EG), during autologous hematopoietic stem cell transplantation (AHSCT) on quality of life (QoL), symptom control and healthcare resource use compared to standard practice (Control Group, CG). We used validated scales on Days 0 (stem cell infusion), + 7 (bone marrow aplasia, acute symptoms) and + 21 (aplasia recovery).ResultsIn 40 patients (20 EG/ 20 CG: 45%/25% female, median age 57.5/59), QoL differed significantly at Day + 7 (EG: median 0.50; CG: -63.00; p < 0.001) and Day + 21 (EG: -2.00; CG: -129.00; p < 0.001). On Day 0, mean FACT-BMT scores were CG/EG: 131/ 89.35, reflecting the pre-transplant intervention of the PCU in EG patients. For pain (EG median 0.00, CG median 2.50; p = 0.01), 45% EG patients used opioids on day 0 (mean 38.5 mg morphine/day/patient). Reduced pain control impacted nutritional support (parenteral nutrition 45% CG, 5% EG; p = 0.08). Hospitalisation duration was longer in CG (median 18.5; EG median 13.00; p < 0.001). Despite the short follow-up and small sample size, PCU and HD collaboration improves QoL and symptom management during acute AHSCT, evident through pain control, analgesia management, reduced parenteral nutrition need and shorter hospital stays.

The Effect of High Intensity Interval Exercise on Platelet Engraftment in Autologous Bone Marrow Transplantation (BMT).

Background: Thrombocytopenia is a frequent complication after hematopoietic stem cell transplantation (HSCT). Although platelet transfusion is the most used treatment for severe thrombocytopenia, it is associated with well-established risks. High-intensity interval exercise (HIIE) results in thrombocytosis. Therefore, this study aimed to reduce thrombocytopenia by increasing platelet count through exercise. Materials and Methods: Twenty lymphoma and multiple myeloma patients were divided into HIIE and control groups. To determine the maximal exercise capacity, patients in the HIIE group performed a graded exercise test. All patients received granulocyte colony-stimulating factor for 5 days,followed by a HIIE trial. After 5 min warm up at 10 to 20% of peak power, patients in the HIIE group performed an HIIE protocol that included 12 intervals of one-minute work at 100% peak power interspersed by one-minute active rest at 20% of peak power. Patients in the control group were seated for the same duration without any physical activity. Two blood samples were taken before and immediately after the trials and were analyzed for measuring complete blood count. Results: Platelet count on the day of platelet engraftment in the HIIE group was significantly higher than in the control group (P=0.02). Single-donor platelet transfusion was significantly lower in the HIIE group than in the control group (P=0.05). Conclusion: Based on the findings of the present study, a short bout of HIIE had a positive effect on platelet engraftment through thrombocytosis and reduced platelet transfusion and its complications, which could be a useful strategy for HSCT patients.

Therapeutic use of autologous hematopoietic bone marrow transplant combined with concentrated platelet in infected surgical wounds: single-center prospective study

The healing wound is the consecutive process of maintaining tissue integrity including inflammatory, proliferative, and remodeling processes. Stem cells can self-renew, and also to differentiate into all cell types, and are involved in physiological regeneration, use of mesenchymal stem cells deriving from the bone marrow with PRP has potentiated the healing process. We conducted a single-arm pilot prospective analytical study was performed on 15 patients whose mean age was 31 years (range: 29–51 years), with refractory abdominal wounds at a private hospital in Iraq from March 30, 2022, to March 2023. Ten days after the stem cell transplant the re-enforcement with PRP subcutaneous injection around wounds. Small papules of granulation tissue appeared over the wound, and tissue granulation increased from 80% (30.26–80.00%) to 100% (81–100%). At the same time, the wound size was reduced by 60% (52.10–78.23%). The follow-up period was 7–24 months, during which no recurrence of the wound was found. In conclusion, the current study is the first to characterize the safety and efficacy of bone marrow-derived stem cells in combination with PRP in the treatment of refractory abdominal wound infection. All patients achieved a 100% healing rate in a short time, and no treatment-related adverse reactions occurred during the treatment.

Pathogenetic parallels and clinical relationships of HIV infection and Hodgkin’s lymphoma

Aim: to show the importance of the features of the development of Hodgkin’s lymphoma (HL) against the background of HIV infection, possible clinical relationships and consequences of simultaneous diseases in patients, as well as complex therapy. Material and methods. The article presents an analytical review of the problem and retrospective data on 63 patients with HIV[1]associated HL (HIV-HL) who were diagnosed with HL in St. Petersburg hospitals in the period 2000–2017. For the diagnosis of HIV-HL, regulated morphological, immunohistochemical, instrumental and laboratory research methods were used, the tumor stage was determined based on the Cotswolds-modified Ann Arbor classification. The diagnosis of HIV infection was confirmed by the detection of specific antibodies to HIV (and the p24 antigen) during serological and enzyme immunoassay of blood, by immune blotting. The number of copies of HIV RNA and the number of CD4 lymphocytes in the blood of patients were determined using commercial test systems approved for use in the territory of the Russian Federation. The analysis of overall survival was performed using the Kaplan–Meyer method. Statistical processing of the research results was performed using statistical programs MS Excel 2010, GraphPad Prism 8 (GraphPad Software, Inc., USA), SPSS version 22.Results. The study group was dominated by men (73%), the median age was 32 years, in 16 (25.4%) patients HIV and HL were detected simultaneously. The number of CD4 lymphocytes &gt; 500 cl/μl at the HL debut was noted in 33.3% of patients, patients with severe immunosuppression prevailed (50–250 cl/μl in 20 (31.7%), 250–500 cl/μl in 11 (17.5%), less than 50 cl/μl in 11 (17.5%). The amount of HIV RNA&gt;400 kop/ml was noted in 82.5%, HIV infection at stages 4B-5 was detected in 89% of cases, at the time of detection of HL ART was performed in 16 patients. EBV coinfection (77.8%), cytomegalovirus (60%), viral hepatitis (55.6%) with a predominance of viral hepatitis C, common opportunistic infections (tuberculosis, pneumocystis pneumonia, toxoplasmosis of the brain, common candidiasis), simultaneously occurring from 1 to 3 infections were observed in 77.8%. Stage IV HL was established in 54%, III — in 22%, II — in 24% of patients, the presence of B-symptoms was confirmed in 73% of cases. The predominant histological variant of HIV-HL was nodular sclerosis (58 patients), mixed[1]cell sclerosis in 4 patients, with lymphoid predominance in 1 case. Extranodal lesions were observed in 34 (54%), complications of the tumor process in 33 (37.5%) patients. 42 (66.7%) patients received antitumor treatment for HL: line 1 according to the ABVD scheme — 85.7% (80% achieved PET-negative complete remission (CR), according to the VEASORR esc or VEASORR schemes — 33.3%; line 2 — according to the ICE or DHAP schemes (n=10). An objective response was noted in 4 patients, PET-negative response in 2 of them, partial PET-positive regression in 2 patients. Progression was observed in 2 people. Autologous bone marrow transplantation was performed in 2 patients (in partial PET-positive regression); line 3 (n=3) — chemoimmunotherapy with bendamustine, gemcitabine (2 patients underwent autologous bone marrow transplantation). The cumulative life expectancy of patients for 1 year and 2 years was 44% and 37%, respectively, 1-year overall survival was 75%, 2-year — 60%. The factors negatively affecting survival and life expectancy were tumor progression and complications, ECOG≥2 (p=0.0001), candidiasis, pneumonia (p=0.001), viral hepatitis B and C (p=0.045), lack of antitumor treatment and ART (p=0.0001), age younger than 40 years, central nervous system damage, the presence of 1 or more concomitant infections (p=0.024). Conclusion. HIV-HL is one of the most common hematological malignancies, characterized by heterogeneity in its manifestations, polymorphism of pathogenetic and clinical features and relationships. During the dispensary supervision of PLHIV, special attention should be paid to the factors of an unfavorable prognosis of the disease, the timeliness of the appointment of ART and the assessment of the risks of developing lymphoproliferative diseases within the framework of the immune system restoration syndrome (IRIS) in order to increase their survival and quality of life. Further research is needed on the pathogenesis, early diagnosis and effective treatment of lymphomas associated with the human immunodeficiency virus

Blood Product Support in Multiple Myeloma Patients Undergoing Autologous Bone Marrow Transplantation May Predict Improved Outcome.

Blood Product Support in Multiple Myeloma Patients Undergoing Autologous Bone Marrow Transplantation May Predict Improved Outcome.

Evaluation of 5-Year Survival Rate of Patients with Multiple Myeloma Undergoing Bone Marrow Transplantation: A Descriptive Study

Background: Multiple myeloma is a progressive and high mortality neoplasm, and the prevalence increases with aging. The main treatment for new cases aged less than 65 years is high-dose chemotherapy with autologous bone marrow transplantation. This study aims to determine the five-year survival rate of patients with multiple myeloma.&#x0D; Methods: In this descriptive-analytical study, 97 patients with multiple myeloma who underwent bone marrow transplantation between 2011 and 2016 were investigated. Then, information related to gender, age at the time of transplantation, the time interval between diagnosis and transplantation, cases of death and, date of death of the studied patients were collected, and the survival of the patients from the date of diagnosis to the end of the study period (five years) was calculated. Data were analyzed using Cox proportional and chi-square tests.&#x0D; Results: Five-year survival of patients was 59.8%. The median overall survival of patients was 54.22 months, which shows that age (p value = 0.003), gender (p value = 0.591), and the time delay between diagnosis and bone marrow transplantation (p value = 0.005) all affect patient survival. There was a significant relationship between the patient's age and the time interval between diagnosis and transplantation with the five-year survival of the patients.&#x0D; Conclusion: As a result, bone marrow transplantation provides a higher survival rate. Also, the effect of the patient‘s age and time interval between diagnosis and transplantation, early diagnosis of the disease and, earlier bone marrow transplantation can bring longer survival for patients.

Hematopoietic stem cell heterogeneity in non-human primates revealed by five-lineage output bias analysis.

Understanding hematopoietic stem cell (HSC) heterogeneity is crucial for treating malignant blood disorders. Compared with mice, we have limited knowledge of the heterogeneity of human HSCs. Fortunately, non-human primates (NHPs) have become the best animal models for studying human HSCs. Here, we employed a public dataset derived from NHP autologous bone marrow transplantation, and focused on a total of 820 HSC clones with reconstitution capacity of all available five lineages (granulocyte, monocyte, B cell, T cell, and natural killer cell) at two time points (11/12 and/or 42/43 months). Intriguingly, unsupervised clustering on these clones revealed six HSC subtypes, including a lymphoid/myeloid balanced (LM-balanced) subtype and five single-lineage-biased subtypes. We also observed that the subtypes of these HSC clones might change over time, and a given subtype could transition into any one of the other five subtypes, albeit with a certain degree of selectivity. Particularly, each of the six subtypes was more likely to turn into lymphoid-biased rather than myeloid-biased ones. Additionally, our five-lineage classification method exhibited strong correlation with traditional lymphoid/myeloid bias classification method. Specifically, our granulocyte- and monocyte-biased subtypes were predominantly attributed to α-HSCs, while LM-balanced, B cell-biased, and T cell-biased subtypes were primarily associated with β-HSCs. The γ-HSCs were composed of a small subset of B cell-biased and T cell-biased subtypes. In summary, our five-lineage classification identifies more finely tuned HSC subtypes based on lineage output bias. These findings enrich our understanding of HSC heterogeneity in NHPs and provide important insights for human research.

Nursing Care of Adolescents Undergoing HSCT

Autologous bone marrow transplant (ABMT), also known as autologous hematopoietic stem cell transplant (HSCT), is a medical procedure where a patient’s own stem cells are collected and later infused back into the patient after high-dose chemotherapy or radiation. This procedure is often used in the treatment of certain cancers, such as neuroblastoma or leukemia, as well as certain non-malignant conditions. Nursing care for a child undergoing autologous bone marrow transplant involves various aspects of physical, emotional and psychosocial support. Here are some key nursing considerations Pre-transplant care education provides age-appropriate education about the transplant process, including what to expect before, during and after the procedure. Educate the child and family about potential side effects, complications and the importance of strict infection control measures. Children undergoing HSCT face lot of challenges and pediatric nurses play a vital role in providing safe and quality care.

Detection of active human cytomegalovirus in patients with multiple myeloma

Abstract: BACKGROUND: Human cytomegalovirus (HCMV) infection is ubiquitous and successfully reactivated in patients with immune dysfunction as in patient with multiple myeloma (MM), causing a wide range of life-threatening diseases. Early detection of HCMV and significant advances in MM management has amended patient outcomes and prolonged survival rates. OBJECTIVES: The aim of the study was to estimate the frequency of active HCMV in MM patients. MATERIALS AND METHODS: This is a case–control study involved 50 MM patients attending Hematology Center, Baghdad Teaching Hospital; 25 of them were newly diagnosed and 25 on treatment compared to 50 of apparently healthy control. HCMV-viral load was measured using a real-time polymerase chain reaction (RT-PCR). RESULTS: Active HCMV was detected in 8 patients out of 50 (16%); 6/25 (24%) in newly diagnosed and 2/25 (8%) on treatment and had autologous bone marrow transplant with mean ± standard deviation of 910 × 1010 ± 210 × 1010, and 32,000 × 1010 ± 1500 × 1010 IU/mL, respectively. HCMV viremia is equally detected in both remission and relapsed cases. CONCLUSION: RT-PCR detected a significant number of MM patients infected by cytomegalovirus compared to healthy individuals. Further studies are needed to verify if this finding has a relation to etiology or disease progression.

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

Sclerosing mesenteritis.

A patient with light chain multiple myeloma and no evidence of disease following autologous bone marrow transplantation, developed asymptomatic mass in the right lower quadrant mesentery, which increased in size and showed FDG uptake on PET CT. The only other change of note on imaging was chronic appendicitis, confirmed on surgery and pathology. Suspecting a neoplastic mass in the mesentery, surgical resection was undertaken but the pathology revealed sclerosing mesenteritis. This rare, non-neoplastic fibro-inflammatory disease, its protean manifestations, disease associations, and treatment are briefly discussed, including the perplexing coexistence with adjacent appendicitis.

Evaluation of the frequency of hepatitis b virus reactivation and the importance of hepatitis b prophylaxis in hematology patients receiving immunosuppressive therapy: a single-center study

Aims: The aim of this study was to evaluate the rate of hepatitis B virus reactivation (HBVr) in hematology patients receiving immunosuppressive therapy in our center and the clinical characteristics of patients with HBVr. We will also investigate the importance of effective prevention of this potentially life-threatening event and management of hepatitis B virus (HBV) prophylaxis. Methods: In this study, hepatitis B prophylaxis and its effects on patients over 18 years of age receiving immunosuppressive therapy in the hematology clinic were analyzed. 122 patients were included in the study. The HBV markers of the patients were determined by the chemiluminescence method. In the study, HbsAg(+) and isolated antiHbc IgG-positive patients received prophylactic antiviral treatment. The differential diagnosis of HBV reactivation and the criteria determined to define HBV reactivation were performed. Clinical characteristics and descriptive information of patients receiving HBV prophylaxis were analyzed using SPSS 25.0. Results: The median age of 122 patients (59.8% male) was 58 years. It was determined that five HbsAg-positive patients had no prior follow-up and did not receive antiviral treatment. 117 patients had isolated anti-HBc IgG positivity. The median duration of prophylaxis was 15 (9- 21.25) months, and the total follow-up period was 19.5 (11.75- 30.25) months. 81.1% of the patients received regular HBV prophylaxis treatment; 59% of them received entecavir, and the rest received tenofovir disoproxil. Bone marrow transplantation was performed in 25 patients. HBV reactivation was detected in only 4 patients (3.3%); one of these patients had received allogeneic and one autologous bone marrow transplantation; and three patients had received chemoimmunotherapy including Rituximab. The diagnoses of the patients with HBVr were acute myeloid leukemia, lymphoma, and chronic lymphocytic leukemia. During the follow-up period, 29 patients (23.8%) died due to their primary disease, but there were no deaths due to HBV reactivation. Conclusion: The data obtained in this study show that effective hepatitis B prophylaxis treatment is successful in preventing HBV reactivation in hematology patients. HBVr was observed in four patients who did not take HBV prophylaxis medication regularly.

Incidence, Clinical Characteristics and Risk Factors for Poor Mobilization of Hematopoietic Stem Cells in a Colombian Bone Marrow Transplantation Unit: A Retrospective Cohort Study

Background: mobilized peripheral hematopoietic stem cells (PHSC) are the main cell source for autologous bone marrow transplantation. Failure to mobilize an appropriate number of PHSC can jeopardize autologous bone marrow transplantation procedure. Objective: our aim was to describe the clinical and demographics characteristics, the incidence of mobilization failure and the prevalence of risks factors for poor mobilization in patients in whom PHSC mobilization were attempted for autologous bone marrow transplantation between January 1st 2017 and 31 December 2022. A univariate and multivariate analysis (binary logistic regression) were done to determinate the association between risk factors and mobilization failure. Results: 129 patients were included , the patients median age was 54 years. Indications for autologous bone marrow transplantation were multiple myeloma in 50,4 %, lymphoma in 46,5 % and systemic sclerosis in 2,3 % of patients respectively. Mobilization was attempted with Filgrastim in 71,1 %, Filgrastim plus Plerixafor in 26,6 % and chemotherapy (Cyclophosphamide) plus Filgrastim in 2,3 % of patients respectively. Mobilization failure occurred in 9,3 % of patients (12 patients) occurring in 11 % of patients who received Filgrastim, in 5,6 % who received Filgrastim plus Plerixafor and in none of patients who received chemotherapy plus Filgrastim. No difference in mobilization failure was found between patients who received Filgrastim monotherapy versus those who received Filgrastim plus Plerixafor ( χ 2 p=0,388, relative risk: 1,8, confidence interval 95% 0,43 - 8,1). Patients who received Filgrastim plus Plerixafor had been treated more frequently (four of more cycles of Lenalidomide) compared with patients who received Filgrastim alone (63,3 % versus 18,7 %, χ 2 p &amp;lt; 0,001, RR=4,01, CI 95 %; 2,32-6,87).The median age of patients was superior in patients who received Filgrastim plus Plerixafor compared with those who received Filgrastim (58 vs 51 years, U Mann Whitney p = 0,02). The median number of treatment lines tended to be superior in patients receiving Filgrastim plus Plerixafor compared to those receiving Filgrastim (2 lines versus 1 line of therapy, U Mann Withney p= 0,054). Patients who had been treated with intensive chemotherapy regimens like DHAP, ESHAP or Hyper CVAD (p=0,004, RR: 4,3, CI 1,5-12,3)) and patients older than 60 years (p=0,018, RR: 3,4 (1,2-9,85)) were significant more prone to mobilization failure in bivariate and multivariate analysis. Conclusion: mobilization failure occurred in 9,3 % of patients , Filgrastim monotherapy was more frequently used, no difference in mobilization failure was found between those who received Filgrastim versus Filgrastim plus Plerixafor, history of treatment with more than 4 cycles of lenalidomide and older age were more frequently in patients who received Filgrastim plus Plerixafor. History of a treatment intensive chemotherapy regimen and being older than 60 years were consistently associated with mobilization failure in univariate and multivariate analysis.

Intermittent Sargramostim Administration Expands Proliferating Naïve T Cells, Tregs, HLA-DR+ PD-L1+ Monocytes and Myeloid-Derived Suppressor Cells: Results from a Randomized Placebo-Controlled Clinical Trial of GM-CSF in Patients with Peripheral Artery Disease

Introduction: Sargramostim (rhuGM-CSF; Leukine ®) is an FDA-approved drug known for mobilizing hematopoietic progenitor cells and expediting hematopoietic reconstitution in patients with acute myeloid leukemia (AML) as well as after autologous and allogeneic bone marrow transplantation. While GM-CSF has been explored as an adjuvant for cancer vaccines due to its ability to promote dendritic cell differentiation and maturation, continuous daily administration of sargramostim has been associated with leukocytosis and adverse side effects. To validate and expand upon our previously published findings that thrice-weekly sargramostim administration in patients with severe peripheral artery disease (PAD) is both well-tolerated and beneficial for claudication symptoms, we conducted a placebo-controlled randomized clinical trial to assess the efficacy of an extended dosing regimen of sargramostim in PAD patients. Data regarding progenitor mobilization kinetics and claudication symptoms will be presented elsewhere. In this analysis, we investigated the impact of intermittent sargramostim dosing on immune cell subsets in the bloodstream, aiming to support the use of this dosing schedule for enhancing adaptive immunity. Methods: Symptomatic atherosclerotic PAD patients were enrolled and randomly assigned to receive either 500 μg/day of sargramostim or placebo via self-administered subcutaneous injections thrice weekly for 3 weeks, for two separate courses 3 months apart. The study was IRB-approved with adverse events and safety signals monitored by an independent Data Safety Monitoring Board. A total of 61 patients (40 receiving sargramostim and 21 receiving placebo) participated in the immune-monitoring sub-study. Blood mononuclear cells were collected at various time points and cryopreserved. Thawed peripheral blood mononuclear cells (PBMCs) were stained using immune cell-specific antibody cocktails, and analyzed by flow cytometry. Statistical significance was determined using the Student's t-test. Results: No dose-limiting leukocytosis or drug-related side effects were observed. As expected, the numbers of white blood cells (WBCs) increased by an average of 68% in the blood of sargramostim-treated patients compared to placebo-treated patients, with peak values reached after 3 weeks of intermittent study drug administration, followed by return to baseline before the next treatment course. Absolute counts of CD3+, CD4+, and CD8+ T cells, B cells, and CD14+ monocytes significantly increased one and two weeks after starting intermittent sargramostim treatment compared to the control group. Notably, sargramostim-treated patients exhibited higher levels of proliferating naïve, Ki-67+ CD4+ T cells (106.83/uL ± 70.28) compared to placebo-treated patients (44.94/uL ± 33.84, p=0.001), as well as increased numbers of naïve Ki-67+ CD8+ T cells (33.05/uL ± 25.43 after sargramostim versus 15.77/uL ± 15.73 for placebo, p=0.01) (Fig. 1, A). However, sargramostim treatment did not influence the quantities of central memory CD4+ and CD8+ T cells. Besides the heightened proliferation of naïve T cells, sargramostim treatment also resulted in a significant increase in the numbers of CD3+CD4+CD25+FoxP3+ Tregs (Fig. 1, A), as well as PD-1-expressing CD4+ and CD8+ T cells, compared to the control group. Moreover, sargramostim treatment led to elevated levels of CD14+HLA-DR+ and CD14+PDL-1+ monocytes, as well as myeloid-derived suppressor cells, 2 and 3 weeks after initiation of treatment, when compared to the control group (Fig. 1, B). Conversely, sargramostim treatment had no impact on the levels of gamma-delta T cells, natural killer (NK) cells, plasmacytoid dendritic cells, or classical dendritic cells. Conclusions: Our findings demonstrate that intermittent dosing with sargramostim is well-tolerated and induces significant but transient increases in the numbers and activation status of T cells in the bloodstream. Sargramostim treatment also increased numbers of proliferating naïve T cells, Tregs, and certain subsets of myelo-monocytic cells with immunosuppressive phenotypes. These results support the use of intermittent sargramostim dosing to avoid excessive leukocytosis and associated adverse effects. Further investigation is warranted to elucidate the clinical implications of these findings in the context of immune modulation.

A Phase II Multicenter Clinical Trial Assessing the Safety and Efficacy of Ixazomib, Pomalidomide and Dexamethasone Combination As Second or Third-Line Treatment for Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma (iPod-790 Trial)

Introduction: Despite significant improvement in the outcomes of early treatment lines in myeloma, most patients (Pts) invariably relapse. As triple and quadruple regimens are being introduced at the upfront setting, many Pts are either triple-class exposed or triple-class refractory (TCE/TCR) early in their disease course. Although novel immunotherapies are emerging with impressive efficacy among TCE/TCR myeloma Pts, their use is currently limited due to potential toxicities, costs and logistic constraints. We report the outcomes of the IPoD-790 clinical trial (NCT04790474), an all-oral regimen: ixazomib (IXA), pomalidomide (POM) and dexamethasone (DEX) (IPd) combination, in Pts with relapsed refractory multiple myeloma (RRMM) who progressed after bortezomib (BTZ), lenalidomide (LEN) and daratumumab (DARA) therapies. Methods: A phase 2, investigator initiated, open-label, single-arm, prospective, multicenter study evaluating the safety, tolerability and efficacy of IPd as a second or third-line combination treatment for TCE RRMM Pts. Pts receive IXA: 3 mg days (d) 1,4,8,11 of 21-d Cycles (Cy) 1-3; 4mg d 1,8,15 of 28-d Cy 4-24. POM 4mg: d 1-14 Cy 1-3; d 1-21 Cy 4-24. DEX 20mg: d 1,2,8,9,15,16 Cy 1-3; d 1,2,8,9,15,16,22,23 Cy 4-24. Treatment continues for 24 cycles, or until disease progression (PD) or unacceptable toxicity (the earliest of the three). After completion of 24 treatment cycles, Pts continue POM DEX as standard of care. The primary endpoint is progression free survival (PFS) according to IMWG criteria. Results: Fifty-five (out of the 60 Pts planned) were enrolled; we report data on 46 Pts who had their first dose between March 2021 and April 2023, further data will be presented at the meeting. The median age was 72 (range: 53-88); 18 (39%) were ≥75 years old; 59% were male, ISS was I/II/II for 48% / 25% and 28% respectively; 59% had high risk FISH cytogenetics (t(4:14), t(14:16), +1q21, del17p) with 14% double-hit. Nine percent had extramedullary disease at study enrollment. Exposure rates to BTZ, LEN and DARA were 100%, 98% and 96%, respectively. Forty-one percent had undergone autologous bone marrow transplantation. Refractoriness rates to BTZ, LEN and DARA were 57%, 91% and 65%, respectively. Thirty-seven percent were TCR. At data cutoff date of 15-Jun-2023, the median follow-up time was 10.4 [95% CI 7.6-13.2] months. Ninety-three percent of the Pts had at least one treatment emergent adverse event (TEAE) and 65% had a TEAE grade 3 or 4. Common (≥ 10%) TEAEs include neutropenia 35% (28% Gr 3 or 4), pneumonia 24% (17% Gr 3 or 4), thrombocytopenia 22% (15% Gr 3 or 4), back pain 22% (2% Gr 3 or 4), asthenia 20% (0% Gr 3 or 4), diarrhea 20% (0% Gr 3 or 4), peripheral edema 20% (2% Gr 3 or 4), COVID19 infection 15% (2% Gr 3 or 4 ), anemia 13% (2% Gr 3 or 4), acute kidney injury (AKI) 13% (7% Gr 3 or 4), rash 13% (0% Gr 3 or 4). At data cut-off date, 31 Pts (67%) discontinued the study treatment; 20 (43%) due to PD, 7 (15%) due to adverse events (including 3 patients with pneumonia, and 1 patient each with COVID19 infection, campylobacter gastroenteritis, upper gastrointestinal bleeding and AKI) and 4 (9%) died (2 cases of pneumonia, 1 COVID 19 infection and 1 cerebro-vascular accident). Overall response rate was 59% (27/46); 8 Pts (17%) achieved complete or very good partial response (CR/VGPR), 19 Pts (41%) achieved partial response (PR) and 12 Pts (30%) had stable disease (SD). The median PFS was 6.6 [95% CI 2.9 - 10.3] months (Figure 1a). Median duration of response (DOR) was 10.8 months. Median OS was not reached; 1-year overall survival was 81.6±6.7% (Figure 1a). One-year OS was significantly better for responders (89.3±7.3%) than non-responders (72.2±10.7%), p=0.015 ( figure 1b). Conclusions: IPd combination with a twice-weekly ixazomib induction provided an all-oral safe and efficacious therapy in triple-exposed RRMM Pts, most of whom were refractory to both DARA and LEN. Response rates and PFS are encouraging, compared to parenteral PI and IMiD combination regimens in TCE/TCR MM, with a favorable safety profile and convenience, especially among an elderly and frail population with relapsed myeloma.

Characteristics and Outcomes of Adolescent, Young Adults, and Adults 40-50 Years Old with Multiple Myeloma: A Single Center Experience

Background Multiple myeloma (MM) is a malignant tumor with abnormal proliferation of plasma cells. Adolescent and Young Adult (AYA) patients are defined as patients between 15-39 years of age. Multiple myeloma is uncommon in non-elderly populations. Its prevalence is only 2% in AYA age group and only 10% in patients 40-50 years old. The feature of MM is not well known or understood in those two age groups. In this retrospective study we describe the clinical characteristics, cytogenetics, prognostic markers, treatments given and outcomes of MM in AYA and 40-50 years old patients. Methods We retrospectively analyzed data from the clinical database of our single tertiary hematology center, The National Center for Cancer Care and Research, Doha, Qatar. This center serves a country's population of about 2,8 million people. All patients diagnosed with MM between the age 50 or less during the period of January 2007 to December 2022 were included. Results Seventy-four patients were diagnosed at our centre with MM before the age of 50 years, total of all MM cases 222 (33%) Males was predominant 55/74 (74.3 %) with a median age of 41 years (range, 15-49). Most of the patients were from Asian 55%. At diagnosis patients had a median hemoglobin of 10.2 g/dl, creatinine 294 umol/L, total protein 90 gm/L, albumin 34.75 gm/L, calcium 2.7 mmol/L, LDH 255 U/L, IgG 2289.75 mg/dl, IgA 424.15 mg/dl, IgM 34.2 mg/dl, FLC-Kappa 1993 mg/L and FLC-Lambda 1177 mg/L. Median of bone marrow filtration by plasma cell was 51 %. Most of the patients presented at advance stages with 44 patient (59%) presented as IIIA Durie Salmon or stage III and IV by ISS 70 %. IgG Kappa most frequent type of MM 18 patients (24%), followed by Free light chain kappa (23%), IgG Lambda (18%) and others including two cases of plasmacytoma (Most recurrent cytogenetics were diploid cytogenetics in 42 patients (57%), while 7 patients (9%) had complex cytogenetics. Twenty-eight patients had spinal cord compression at single or multiple levels ( thoracic were most common site 20%) while 3 patients had pathological fractures. Bortezomib based regimen is most one used to treat our patients. Daratumumab- Velcade, Revlimid, and dexamethasone (D-VRD) was used for 35 patients (74%) and Velcade,Cyclophosphamide and Dexamethasone VCD in 20 patients (27%). The first response to treatment showed completed remission (CR) in 35 patients, very good partial remission in 10 patients, partial response in 9 patients, four patients either refractory or primary refractory disease and one patient with stable disease. Thirty -five patients (48%) underwent their first autologous bone marrow transplant ASCT. A total of 8 patients underwent second ASCT and one patient underwent third ASCT. After a median duration of follow up of 6.25 years and 72 % of the patients were still alive. We compared the characteristics and outcome for the AYA group (18-39) with patient age group 40 to 49 years. Although there was no statistical significance difference between the two groups regarding overall survival (p=0.21) , the older group had more cases of spinal cord compressions and more cases of refractory disease. Patient characteristics are described in Table 1. Conclusion One third of MM patients in our center are younger than 50 years. These patients tend to present with advanced stage and serious manifestation such as spinal cord compression. IgG kappa and free light chain are the most common myeloma type in this cohort. D-VRD is the most used protocol with a good response rate. Patient characteristics and treatment outcomes are the same for AYA patients compared with patients 40-49 years old (p=0.21). Patients who received first transplant had better OS compare the those who didn't (p0.01)