Autologous Peripheral Blood Hematopoietic Stem 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.

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.

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.

Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients

To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

Efficacy of Activated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

To compare the efficacy of activated autologous bone marrow and peripheral blood hematopoietic stem cell transplantation (Auto-HSCT) and matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for the first complete remission of adult acute myeloid leukemia (AML-CR1). For 86 adult patients with first complete remission of AML who underwent auto-HSCT (41 cases) and MSD-HSCT (45 cases) in our hospital from June 2012 to June 2020, the patients were treated with modified MAC ［Malflane 160 mg/(m2·d), -3 days, Ara-C 2 g/(m2·2), -3 days 21∶00, -2 days 9∶00, CTX 60 mg/(kg·d),-3 d, -2 d］, the stem cells were activated by IL-2 (1 000 U/ mL), IFN-α (100 U/ mL) and IFN-γ (100 U/ml). The overall survival (OS), leukemia free survival (LFS), cumulative incidence of recurrence (CIR) and non-recurrence mortality (NRM) of patients with different types of transplantation were compared. The 3-year OS rates of Auto-HSCT group and MSD-HSCT group were 75% and 69.5%, and the 3-year LFS rates were 70.6% and 82.4%, respectively. There was no statisticaly significant difference in the 3-year OS rates of low risk, medium risk and high risk patients in the Auto-HSCT and MSD-HSCT group (90.2% vs 87.5%, 68.4% vs 68.8%, 28.6% vs 53.3%), the LFS rates of low risk, medium risk and high risk patients in the auto-HSCT and MSD-HSCT group were 90.2% and 87.5%(P=0.838), 71.8% and 91.7%(P=0.184), 0 and 67.5%(P=0.027), respectively. The NRM of Auto-HSCT and MSD-HSCT group were 4.9% and 20% (P=0.036), and CIR were 24.4% and 13.3% (P=0.188). Univariate analysis showed that the survival time of patients was significantly correlated with the number of CR courses and disease risk stratification (P=0.005, P=0.000). Cox multivariate analysis showed that disease risk stratification was an independent risk factor affecting OS (P=0.001). For adult patients with primary AML-CR1, Auto-HSCT is safe and effective. In the absence of sibling donor, Auto-HSCT can be regarded as an effective post-remission treatment for patients with intermediate risk AML-CR1.

A Multicenter, Single-Arm, Prospective Phase II Study of Orelabrutinib Combined with High-Dose Methotrexate and Rituximab Sequential Autologous Hematopoietic Stem Cell Transplantation in Newly-Dignosed Primary Central Nervous System Lymphoma

Background: Primary central nervous system lymphoma (PCNSL) is primarily large B-cell lymphoma (accounting for nearly 95% of central lymphomas). Current treatments, including surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results, especially in the elderly. High-dose methotrexate (MTX) based treatment is the current standard treatment, but the long-term survival rate of young patients is still less than 50% even after autologous transplantation. Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been tested in multiple clinical trials for PCNSL, as a single drug achieved an objective response rate (ORR) of 50-70% and a CRR of 20%-40% in relapsed and refractory PCNSL, while combination therapy can achieve an ORR of 80% and a CRR of 50%. However, ibrutinib efficacy is less than half a year and has poor selectivity. Owing to its off-target inhibition effect, the incidence of serious adverse reactions such as bleeding and atrial fibrillation in patients increases, leading to dose reduction or drug withdrawal, which makes patients unable to continue treatment. Orelabrutinib is a new-generation BTK inhibitor, that has been rationally optimized in molecular structure, which makes its binding with BTK more durable, more stable, more specific, less off-target effect, and higher BBB pass rate and better safety. In addition, a retrospective article published recently showed that obrutinib monotherapy was more effective and well-tolerated in patients with r/r PCNSL. Herein, we combined rituximab, MTX, and ibrutinib for induction therapy, finally through autologous hematopoietic stem cells consolidation therapy or lenalidomide or obrutinib maintenance treatment, to evaluate toxicity and to improve efficacy. This study is registered with Chictr.org.cn, number ChiCTR2200061485. Methods: The study is a multicenter, single-arm, prospective phase II study, conducted at Shengli Oilfield Central Hospital and Shandong Cancer Hospital. Patients diagnosed with Newly Diagnosed PCNSL by biopsy of brain lesion, systemic immunology, bone marrow, and a CSF examination, et al, and be suitable for the immunochemotherapy, were enrolled in the clinical trial. The Orelabrutinib -based ROM regimen consists of rituximab 375mg / m 2 on day 0. MTX 3.5g/m 2 on day1, and Orelabrutinib 150mg once daily on day1 to day 28. Every 28 days is a cycle of treatment. After 4-cycles of ROM induction therapy, patients who achieved CR/CRu/PR received autologous peripheral blood hematopoietic stem cell transplantation (HSCT) or the extra 2 cycles of ROM regimen as consolidation therapy. Orelabrutinib or lenalidomide monotherapy was prescribed as maintenance therapy, according to the willingness of patients until the disease progresses. The primary endpoint was the safety and efficacy of this regimen in newly diagnosed with PCNSL. Results: There were a real of 10 patients enrolled in this clinical trial, between July 2021 and May 2022. All the patients were pathologically DLBCL, including 7 non-GCB subtypes and 3 GCB subtypes. The median follow-up time was 6.5 (1-12) months up to June 30, 2022. After 4 cycles of ROM induction therapy, complete metabolic remission (CMR) was achieved in 5 patients (50%), partial response (PR) in 5 patients (50%), and the overall response rate (ORR) of induction therapy was 100% (Figure 1). Among responders, 3 (33%) received HSCT, 1 (10%) received RT and 5 (50%) received extra 2 cycles of ROM regimen as consolidation therapy. After the consolidation therapy, 90% of patients (9/10) received maintenance therapy, including 5 who received lenalidomide and 4 who received ibrutinib. The median progression-free survival (PFS) and overall survival (OS) were not achieved. The safety of Orelabrutinib -based regimens have also been evaluated. No grade 4 adverse events were observed. Grade 3 hematologic toxicity included lymphopenia in 1 case and neutropenia in 3 cases. Conclusions: Our data preliminaries indicate that ROM is efficacious and well-tolerated as a first-line regimen in newly diagnosed PCNSL and might effectively improve the survival of these patients. These combined therapies offer a potential new therapeutic strategy. More patients and longer follow-ups are necessary to confirm our conclusion. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Day 100 Peripheral Blood Natural Killer Cell/CD14+HLA-DR- Ratio Predicts Clinical Outcomes in Lymphoma Patients Treated with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Day 100 Peripheral Blood Natural Killer Cell/CD14+HLA-DR- Ratio Predicts Clinical Outcomes in Lymphoma Patients Treated with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation.

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation.

Long-term follow-up of autologous peripheral blood hematopoietic stem cell transplantation for refractory lupus nephritis-a series study of 20 patients.

Autologous hematopoietic cell transplantation (ASCT) improves immunologic homeostasis in autoimmune diseases. ASCT-treated refractory lupus nephritis (LN) has been reported. Nevertheless, the long-term outcome of patients with refractory LN after ASCT remains unknown. This study reports the outcomes of 20 refractory lupus patients with 10-year of follow-up after receiving ASCT. Twenty-two patients with LN refractory to immunosuppressive therapy were enrolled. Twenty patients were examined closely and two cases died within 100 days after ASCT. Hematopoietic cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of intravenous cyclophosphamide, rabbit antithymocyte globulin, methylprednisolone, and G-CSF. All immunosuppressive therapies were discontinued at the start of mobilization and corticosteroids were tapered rapidly after ASCT. Data was collected from 22 patients with refractory LN treated by ASCT. 59% were female, duration of lupus before ASCT was 46 (33-71) months, and median duration of follow-up after ASCT was 89.5 (56-108) months. 20 long-term followed up patients had an average follow-up time of 92 months (63.25-109.5). Eighteen patients achieved complete remission, one patient reached partial remission, one patient without remission started peritoneal dialysis at month 12, and one patient received short-term renal replacement therapy before ASCT started hemodialysis at 84 months after transplantation. Nine patients relapsed 10 times during the follow-up, and three patients received rituximab. Two patients relapsed during pregnancy after complete response and the Apgar scores of infants were 9 and 10, respectively. All nine patients received glucocorticoids and immunosuppressive medication after relapse and responded again. The 10-year overall survival, 10-year disease-free survival rate, and 10-year renal survival were 100%, 35%, and 90%, respectively. The rate of relapse was 45%. Complications included hypocytosis, infection, B-type insulin resistance syndrome, and monoclonal immunoglobulinemia. This study suggests ASCT is effective and safety in treating refractory LN and is beneficial to improve their long-term outcomes.

Gastrointestinal Bleeding Secondary to High-Dose Melphalan Pretreatment in Patients with Multiple Myeloma Was Associated with the Mode of Melphalan Administration.

Objective To analyze the characteristics of gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma. Methods Between 1 January 2016 and 31 October 2021, 26 patients with multiple myeloma after autologous peripheral blood hematopoietic stem cell transplantation with high-dose melphalan pretreatment were recruited. They were assigned to either the oral administration group or the intravenous administration group according to the administration modes, or to either the gastrointestinal bleeding group or the nongastrointestinal bleeding group. Analyses were performed based on the differences in general gastrointestinal symptoms and hemorrhage between different administration modes and on the differences in the general gastrointestinal symptoms, platelet alterations, and the intestinal microecology before pretreatment between patients with and without gastrointestinal bleeding. Results Of the 26 included patients, heavy secondary gastrointestinal bleeding was found in 6 patients with intravenous pretreatment. In patients given intravenous melphalan, those with gastrointestinal bleeding showed more pronounced general symptoms such as nausea and vomiting versus those without. There was no significant difference in platelet alterations between the two groups. Gastrointestinal bleeding was associated with more significant microecological disturbances than no bleeding. Conclusion Gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma was associated with the mode of melphalan administration, adverse symptoms at pretreatment, and the intestinal microecology prior to pretreatment. Thus, improvement of the intestinal microecology prior to pretreatment and mitigation of adverse gastrointestinal symptoms during pretreatment may contribute to a lower incidence of secondary gastrointestinal bleeding and enhanced transplantation safety.

Impact of autograft-absolute lymphocyte count on survival in double/triple hit lymphomas post-autologous stem cell transplantation

The autograft absolute lymphocyte count (A-ALC) ≥0.5 × 109 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC has not be tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. With a median follow-up of 20.4 months (range, 0.4-94.5 months), DHL/THL patients infused with A-ALC ≥0.5 x 109 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117–0.539, p < 0.0004) and PFS (HR = 0.347, 95%CI 0.160–0.753, p < 0.007). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.119, 95%CI 0.030–0.473, p < 0.003) and PFS (HR = 0.400, 95%CI 0.189–0.850, p < 0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL. Our current practice for lymphoma patients is to collect enough stem cell but also A-ALC to improve clinical outcomes post-APBHSCT.

A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs.

In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

Immunologic Autograft Engineering: 13 Years Follow-up

Our group published a double blind, randomized phase III study (Porrata et al, BBMT 2016; 22: 1017-1023) showing that the infusion of autograft absolute lymphocyte count (A-ALC) ≥ 0.5 x 10 9 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, a limitation of the study was the short-term follow-up duration of two years post-APBHSCT. To assess if the A-ALC still provide survival benefit we looked at the 121 lymphoma patients enrolled in the phase III from December 10, 2007 until October 12, 2010 survival outcomes with a longer follow-up duration of up to 13 years post-APBHSCT. Since the accrual for the study, 52 patients had died of recurrence lymphoma, 4 patients of therapy-related acute myelogenous leukemia, 3 patients of unknown causes, 1 patient of acute respiratory distress syndrome, 1 patient of anaplastic astrocytoma, and 1 patient of septic shock. The current median follow-up is 86 months (range: 2.1-158.1 months) for the entire cohort and 127.8 months (range: 5.9-158.1 months) for patients still alive. Patients infused with an A-ALC ≥ 0.5 x 10 9 cells/kg continue to experience superior overall survival (OS) (HR = 0.392, 95%CI 0.224-0.687, P < 0.001) and progression-free survival (PFS) (HR = 0.413, 95%CI 0.253-0.677, P < 0.0004). The 10-year OS rates for the A-ALC ≥ 0.5 x10 9 cells/kg patients was 70% (95% confidence interval [CI], 55%-81%) and for the A-ALC < 0.5 x10 9 cells/kg patients was 36% (95% CI, 25%-49%) (Figure 1A). The 10-year PFS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 57% (95% CI, 43%-70%) and for the A-ALC < 0.5 x10 9 cells/kg group was 28% (95% CI, 19%-40%) (Figure 1B). Autograft lymphocyte subset analysis including autograft-CD3 (A-CD3), autograft CD4 (A-CD4), autograft CD8 (A-CD8), and autograft natural killer cells (A-NK), showed that the infusion of A-NK was a predictor for OS (HR = 0.518, 95%CI 0.292-0.919, P < 0.02) and PFS (HR = 0.393, 95%CI 0.230-0.670, P < 0.0006). The 10-year OS rates for the A-NK ≥ 0.09 x10 9 cells/kg patients was 67% (95% confidence interval [CI], 50%-80%) and for the A-NK < 0.09 x10 9 cells/kg patients was 42% (95% CI, 31%-54%) (Figure 1C). The 10-year PFS rates for the A-NK ≥ 0.09 x10 9 cells/kg group was 59% (95% CI, 43%-73%) and for the A-NK < 0.09 x10 9 cells/kg group was 32% (95% CI, 23%-44%) (Figure 1D). Both the A-ALC and A-NK were independent predictor for OS [ A-ALC: HR = 0.367, 95%CI 0.195-0.690, P < 0.001) and A-NK: HR = 0.411, 95%CI 0.275-0.892, P < 0.01] and for PFS [ A-ALC: HR = 0.477, 95%CI 0.271-0.840, P < 0.01) and A-NK: HR = 0.490, 95%CI 0.266-0.903, P < 0.02]. With a longer follow-up of 13 years, this study shows that the infusion of A-ALC continues to provide better clinical outcomes to lymphoma patients undergoing APBHSCT. These study findings support our standard practice changed of not only collecting CD34 stem cell for hematologic engraftment, but also A-ALC for lymphoma patients undergoing APBHSCT to improve clinical outcomes. Further, autograft immune effector studies are warranted such as A-NK to develop a more immunocompetent targeted autologous graft verus tumor effect. [Display omitted] DisclosuresAnsell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.

Ibrutinib in Combination with Rituximab and High-Dose Methotrexate in Newly Diagnosed Primary Central Nervous System Lymphoma Patients

Ibrutinib in combination with rituximab and high-dose methotrexate in newly diagnosed primary central nervous system lymphoma patientsYixian Guo, Xiaoxi Lan, Xiaoli Chang, Guoxiang Wang, Dongmei Zou, Li Su, Wanling SunDepartment of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. ChinaCorresponding author: Wanling Sun, M.D. & Ph.D.Email: wanlingsun@xwhosp.orgBackground: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma. Most PCNSL are pathologically classified as diffuse large B-cell lymphoma (DLBCL). In addition to the importance of high-dose systemic methotrexate (HD-MTX), there is no consensus on the optimal composition of induction and consolidation therapy for newly diagnosed PCNSL. BTK inhibitors are the second-line recommended choice in relapsed of refractory cases. In this study, we described our institutional experience with the oral BTK inhibitor, ibrutinib, combined with rituximab and HD-MTX (I-RM regimen) in newly diagnosed PCNSL. This study is registered with Chictr.org.cn, number ChiCTR1900027811.Methods: The study was a phase 1, investigator-initiated, clinical trial being conducted at Xuanwu Hospital, Capital Medical University . Patients definitely diagnosed as PCNSL-DLBCL by biopsy of brain lesion, systemic imageology, bone marrow and CSF examination, et al, and be suitable for the immunochemotherapy,were enrolled the clinical trial. The next-generatioin sequencing of the lesion tissue were used to detect hot spot mutations evolved in B cell lymphoma. The ibrutinib-based I-RM regimen consists of rituximab 375mg / m 2 on day 0, MTX 3.5g/m 2 on day1, and ibrutinib 560mg once daily starting from plasma MTX concentration <0.1umol/L to day 28, every 28 days is a cycle of treatment. After 4 cycles of I-RM induction therapy, patients who achieved CR/CRu/PR received autologous peripheral blood hematopoietic stem cell transplantation (HSCT) or the extra 2 cylces of I-RM regimen as consolidation therapy. Ibrutinib or lenalidomide monotherapy was prescribed as maintenance therapy, according to the willingness of patients until the disease progresses. The primary end point was the safety and efficacy of this regimen in newly diagnosed PCNSL.Results:There were totally16 patients enrolled in this clinical trial, between April 2018 and December 2020 (Table 1). All the patients were pathologically DLBCL, including 14 non-GCB subtypes and 2 GCB subtypes. The commonest hot spot mutations were PIM1 (68.75%), MYD88 (43.75%), and CD79B (37.50%). The median follow-up time was 24.5 (6-37) months up to June 30, 2021. After 4-cycles of I-RM induction therapy, CR were achieved in 8 patients (50%), PR in 7 patients (44%), and progressive disease in one patients(6%) who quit the clinical trial and transferred to other regimen，and the ORR of induction therapy was 94%. Among 15 responsers, 5 (33%) received HSCT and 10 (67%) received extra 2 cylces of I-RM regimen as consolidation therapy. After the consolidation therapy, 93% patients (14/15) received maintenance therapy, including 6 received lenalidomide and 8 received ibrutinib. Relapse happened in 2 patients during the maintenance therapy, including 1 death due to the progressed disease (Table 2). The median PFS and OS were not achieved, and the estimated 3-year OS and PFS were 88.9% and 86.5%, respectively (Figure 1). No grade 4 adverse event was observed. The grade 3 hematologic toxicities included lymphopenia in 3 cases and neutropenia in 1 case .The grade 3 non-hematologic toxicities including hypertension in 1 case and increased serum creatinine in 1 case.Conclusions: Our data preliminarily indicates that I-MR is active and safe as a first-line regimen in newly diagnosed PCNSL and might effectively improve the survival of these patients. More patients and longer follow-up are needed to confirm our conclusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autograft-Absolute Lymphocyte Count Infusion Predicts Survival in Double/Triple Hit Lymphomas Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

The autograft absolute lymphocyte count (A-ALC) ≥ 0.5 x 10 9 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC ≥ 0.5 x 10 9 cells/kg has not been tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC ≥ 0.5 x 10 9 cells/kg is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. Of the 77 patients, 62 patients were classified as DHL and 15 patients as THL. Of the DHL, 82 % (52/68) had the MYC/BCL2 and 16% (10/62) the MYC/BCL6 rearrangements. Dividing the cohort into two groups (A-ALC ≥ 0.5 x 10 9 cells/kg and A-ALC < 0.5 x 10 9 cells/kg), both groups were balanced in regard to de novo versus transformed histology (p = 0.3), cell of origin (p = 0.6), DHL and THL (p = 0.6), MYC/BCL2; MYC/BCL6; and MYC/BCL2/BCL6 rearrangements (p = 0.6), first line chemotherapy (p = 0.2), salvage chemotherapy (p = 0.5), disease status prior to APBHSCT (CR1, CR, and PR) (p = 0.07), stem cell mobilization (Plerixafor versus not) (p = 0.6), and infusion of CD34 count (p = 0.2). With a median follow-up of 20.4 months (range, 0.4-94.5 months) for the entire cohort and with a median follow-up of 33.5 months (range, 3.5-94.5 months) for the patients that remained alive, DHL/THL patients infused with A-ALC ≥ 0.5 x 10 9 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117-0.539, P < 0.0004) and PFS (HR = 0.347, 95%CI 0.160-0.753, P < 0.007). The 5-year OS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% confidence interval [CI], 52%-87%) and for the A-ALC < 0.5 x10 9 cells/kg group was 18% (95% CI, 7%-39%) (Figure 1A). The 5-year PFS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% CI, 59%-85%) and for the A-ALC < 0.5 x10 9 cells/kg group was 13% (95% CI, 5%-33%) (Figure 1B). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.178, 95%CI 0.052-0.614, p <0.005) and PFS (HR = 0.400, 95%CI 0.189-0.850, p <0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL patients undergoing APBHSCT. Our current practice for all lymphoma patients is not only to collect enough stem cell for hematologic engraftment, but also A-ALC ≥ 0.5 x 10 9 cells/kg to improve clinical outcomes post-APBHSCT. [Display omitted] DisclosuresAnsell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

High-dose Chemotherapy in Germ Cell Cancer Patients With Brain Metastases: Experience of an Expert Center.

Germ cell tumor (GCT) patients with brain metastases (BM) have a poor prognosis and high risk of treatment failure. Optimal therapies for these patients remain controversial. The aim of this study was to report the outcomes of all GCT patients with BM treated with high-dose chemotherapy (HDCT) in our French expert center for GCT. We carried out a retrospective study of 35 GCT patients with BM who were treated from 2003 to 2019 with HDCT, followed by infusions of autologous peripheral blood hematopoietic stem cells. The overall survival at 2 years was 36.9% (95% confidence interval, 19.7-54). The median overall survival was 12 months and the median progression-free survival was 8 months. No variables were associated with better survival in the univariable analysis. Among the 35 patients included in our study, 31 completed HDCT and 4 stopped treatments after mobilization. Eleven patients (11) showed favorable responses (complete, partial, or stable disease) to HDCT and 20 patients died of disease progression (17) or toxicities (3). Among the 11 patients with favorable responses to HDCT, 8 (72.7%) had metachronous BM, mostly isolated. The majority of these patients did not receive local treatment at diagnosis or at relapse. Together, our study reveals that GCT patients can experience long-term survival even in the presence of BM. Metachronous BM can also be cured with HDCT even in the absence of local treatment. Biological and radiologic responses to mobilization could be a predictor of favorable responses to HDCT.

Infused Autograft-Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B-Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched-Control Study

Introduction Day 15 absolute lymphocyte count (ALC-15) recovery after autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) is recognized as a prognostic factor for survival. ALC-15 recovery is directly dependent on the amount of collected and infused autograft-absolute lymphocyte count (A-ALC). Our group published a double-blind phase III study which showed that patients infused with an A-ALC ≥ 0.5 x 109 cells/kg experienced superior survival post-APBHSCT. Based on the results from our phase III study, on April 1, 2017, our Bone Marrow Transplant Program changed our standard clinical practice to collect an A-ALC ≥ 0.5 x 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. To continue to assess the prognostic ability of A-ALC, we evaluated the overall survival (OS) and progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) patients that underwent APBHSCT after April 1, 2017 compared with a matched-control group in a 1:1:1 ratio with DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg or an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1, 2017. Methods Eight-five consecutive DLBCL patients after our practice changed on April 1, 2017 received an A-ALC ≥ 0.5 x 109 cells/kg. For each DLBCL patient infused with an A-ALC ≥ 0.5 x 109 cells/kg after April 1, 2017, the set of potential controls was restricted to those DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg and an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017 . Within this group of potential controls, the subjects were chosen who best matched for the cases in terms of clinical risk variables, including gender, age, stage, lactate dehydrogenase (LDH), performance status, extra-nodal disease, International prognostic index (IPI), and disease status prior to APBHSCT (complete or partial response), using the GREEDY algorithm. Cases were defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg starting from April 1 2017. Control 1 was defined as DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg prior to April 1 2017. Control 2 was defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017. We truncated the survival follow-up to 3 years starting from the date of transplant to match follow-up time between cases and controls. Both matched cases and control groups patients received BEAM conditioning. This retrospective study was approved by the Mayo Clinic Institutional Review Board according to the regulation of the Declaration of Helsinki. Results Cases, control 1 and control 2 were balanced to the clinical risk variables; age (p = 0.8); gender (p = 0.9); LDH (p = 0.6); stage (p = 0.3); performance status (p = 0.5); extra-nodal disease (p = 0.2); IPI (p = 0.6); and clinical status prior to transplant (p = 0.2). Figure 1A showed the OS and figure 1B the PFS. Both the cases and control 2 showed superior OS and PFS in comparison to control 1. Cases and control 2 showed overall similar OS and PFS. Multivariate analysis including all patients continue to depict the A-ALC ≥ 0.5 x 109 cells/kg as an independent predictor for OS (HR = 0.382, 95%CI=0.241-0.605, p &amp;lt; 0.0001) and PFS (HR = 0.437, 95%CI = 0.279-0.629, p &amp;lt;0.0001). Subgroup analysis, including all patients, shows superior OS and PFS for patients infused with an A-ALC ≥ 0.5 x 109 cells/kg for each of the following clinical variables: age [&amp;gt; 60 years: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001) or ≤ 60 years: OS (p &amp;lt;0.01); PFS (p , 0.02)]; extra-nodal disease [&amp;gt; 1: OS (p &amp;lt;0.008); PFS (p &amp;lt;0.01) or ≤1: OS (p &amp;lt; 0.001): PFS (p &amp;lt;0.0005)]; IPI [&amp;gt; 2: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02) or ≤ 2: OS (p &amp;lt;0.0008); PFS (p &amp;lt;0.0006)]; LDH [abnormal: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.005) or normal: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.002)]; performance status [&amp;gt; 1: OS (p &amp;lt;0.04); PFS (p &amp;lt;0.03) or ≤ 1: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001)]; stage [I/II: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.006) or III/IV: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.001)]; response prior to transplant [complete response: OS (p &amp;lt;0.0007); PFS (p &amp;lt;0.0001) or partial response: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02)]. Conclusion Our match-control study continues to support the results of our Phase III study showing that the infusion of A-ALC is a prognostic factor for survival of DLBCL patients undergoing APBHSCT. Our studies support the practice of not only collecting enough stem cells (i.e., CD34) for hematologic engraftment, but also enough immune effector cells (i.e., A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT. Figure 1 Disclosures Ansell: Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Trillium: Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding.

Long-Term Results of the Treatment of Persons with Hodgkin's Lymphoma in a Resource-Constrained Setting: Real-World Data from a Single Center

Background: Hodgkin's lymphoma (HL) is the model of curative care with radiation therapy, combination chemotherapy, staging approaches, peripheral blood stem cell transplantation, and immunotherapy. However, the value of the novel anti cancer drugs has been recently analyzed and questioned in view of the results in the real improvement of overall survival (OS). Material and methods: All consecutive patients seeking medical care after 1986 in our institution as a result of HL and followed for at least 3 months were entered in the study. A diagnosis of HL was based on the histological study of a pathology specimen, mainly a lymph node; the same pathologist analyzed all the specimens and defined the histological subtype. Clinical stage was defined according to the Ann Arbor classification. Bone marrow biopsies were done only in patients with clinical stages III or IV. Computed tomography (CT) scans were done in all cases, prior to starting the treatment. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans were performed since 2002. Between 1986 and 1997, patients were treated with MOPP, and after 1997 with ABVD as frontline therapy. For stages I and II, four cycles of chemotherapy were delivered and a computerized tomography (CT) scan was performed; if lymph node enlargement were present at this point in time, four additional cycles were given, whereas two additional cycles were given if the CT scan was negative. For stages III and IV, the CT scans were performed at the end of six cycles and two or four more cycles. Mediastinal radiotherapy was delivered only to persons with a positive FDG-PET scan at the end of the treatment. Patients showing activity after these treatments were considered as refractory and treated with four courses of ICE (ifosfamide, carboplatin and etoposide). Autologous or allogeneic peripheral blood hematopoietic stem cell transplants (HSCT) were given to refractory patients after achieving a complete remission (CR): High-dose melphalan (200mg/m2) was employed in autologous transplants, whereas cyclophosphamide, fludarabine and busulfan were employed in allogeneic transplants, all of them from HLA-identical siblings. After the completion of the treatment, patients were every two months for one year and every four months later on. No FDG-PET scans were done during the follow up, unless clinically indicated. Results: Among 91 patients with HL identified between 1986 and 2020, 88 were followed three months or more and were included in the analysis. There were 37 females and 51 males. The median age was 29years (range5-73years). There were 62 patients with nodular sclerosing HL (70%), 19 mixed cellularity (HL), 2 lymphocyte depleted HL, and one lymphocyte predominant HL; in 4 cases the histologic variant could not be defined. According to Ann Arbor classification, 5 patients were found in stage I, 48 in stage II, 19 in stage III and 16 in stage IV. Ten patients presented with a mediastinal mass larger than 10 cm. in the chest X-ray film. Three cases presented with relapsed disease. Patients have been followed for a median of 114 months (range4-402). 44 patients are alive, 10 have died and 34 were lost to follow-up. Median OS for all the patients has not been reached, being above 402 months, the OS at 310 months is 88% and at 402 months 77%. Median OS has not been reached and is above 94, 109, 90 and 98 months for stages I, II, III and IV, respectively (p=0.2). The 310-month OS was 83% for patients treated with MOPP and 88% for those treated with ABVD (HR:0.76, 95% CI 0.2-2.8; p=0.6).Sixteen patients (18%) were refractory to the treatment and 9 (10%) relapsed; they were treated with ICE followed by HSCT (autologous 15 patients and allogeneic 10 patients). Patients who underwent auto-HSCT had a median survival of 329.1 months and an OS of 92.3%, whereas those given allo-HSCT had a median survival of 59.3 months and an OS of 45.7% (HR0.2, 95%CI 0.04-1.3, p=0.057). The OS of patients given or not HSCT was 73.5% and 92.9% at 266 and 404 months, respectively (HR4.09, 95%CI 1.0-16.6, p=0.01). The OS was similar. The causes of death were breast carcinoma in 2 cases, liver carcinoma in one and uncontrolled lymphoma activity in the remaining. Conclusion: HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, irrespective of clinical stage. Disclosures No relevant conflicts of interest to declare.

Efficacy of autologous versus allogeneic peripheral blood hematopoietic stem cell transplantation in non-high-risk acute myeloid leukemia patients in first complete remission

Efficacy of autologous versus allogeneic peripheral blood hematopoietic stem cell transplantation in non-high-risk acute myeloid leukemia patients in first complete remission