Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation Research Articles

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.

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.

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.

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.

A Clinicopathological Study of Cytomegalovirus Lymphadenitis and Tonsillitis and Their Association with Epstein-Barr Virus.

IntroductionHistopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation.MethodsWe reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied.ResultsFor lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4–5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein–Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers.ConclusionsCytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance.Graphic abstract

Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial.

Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited. The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma following autologous peripheral blood HSCT were assessed. Eighty patients (age: 18-68years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25μg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated. Median time to ANC engraftment (≥0.5 × 103/μl: 10.0 vs. 11.0days; P = 0.98) and PC engraftment (≥20.0 × 103/μl: both 14.0days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/μl: 13.0 vs. 20.0days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/μl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/μl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72). Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT. Graphical abstract Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.

Reduction of Opioid Use by Acupuncture in Patients Undergoing Hematopoietic Stem Cell Transplantation: Secondary Analysis of a Randomized, Sham-Controlled Trial.

To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation. Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P = 0.86). Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients.

Acupuncture for symptom reduction in myeloma patients undergoing hematopoietic stem cell transplantation: A randomized, sham-controlled trial.

8021 Background: Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for a number of hematologic malignancies, but is associated with a high symptom burden for patients. We conducted a randomized sham-controlled trial to evaluate the preliminary efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. Methods: Adult patients with multiple myeloma undergoing high dose melphalan followed by autologous peripheral blood HCT were randomized to receive either true or sham acupuncture once daily for five days starting on the day after chemotherapy. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days after transplantation. Results: Among 60 participants, symptoms that are significantly reduced by true acupuncture more than sham acupuncture at 15 days include the following: nausea, lack of appetite, and drowsiness (p = 0.042, 0.025, and 0.010, respectively). Patients receiving sham acupuncture were more likely to increase use of pain medication post-transplantation (odds ratio 5.31, p = 0.017). Acupuncture was well tolerated with few attributable adverse events. Conclusions: True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing autologous HCT, and to reduce the use of pain medications. These findings need to be confirmed in a future definitive study. Clinical trial information: NCT01811862.

65 - Infusion of Autograft Natural Killer Cells/CD14+hla-DRDIM Myeloid-Derived Suppressor Cells Ratio Predicts Survival in Non-Hodgkin Lymphoma Undergoing Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation (APHSCT)

65 - Infusion of Autograft Natural Killer Cells/CD14+hla-DRDIM Myeloid-Derived Suppressor Cells Ratio Predicts Survival in Non-Hodgkin Lymphoma Undergoing Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation (APHSCT)

Sustained Natural Killer Cell Recovery Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation Predicts Survival in Non-Hodgkin's Lymphoma

AbstractOur group recently reported a Phase III clinical trial (Porrata et al. Biology of Blood and Marrow Transplantation 2016; 22: 1017-1023) demonstrating that the infusion of the autograft-absolute lymphocyte count (A-ALC) and autograft natural killer cells (A-NKC) are survival prognostic factors in non-Hodgkin lymphoma (NHL) patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). A limitation of our Phase III clinical trial was the short-term follow-up of just two years. Therefore, we evaluated longer follow-up and assessed the role of the infused A-ALC, infused A-NKC, and peripheral blood absolute natural killer cell count (ANKC) recovery on survival post-APBHSCT. Of the 122 patients that participated in the Phase III trial, 111 patients were able to complete APBHSCT and included in the current study. With a median follow-up of 57.2 months (range: 2.1-84.6 months), superior overall survival (OS) and progression-free survival (PFS) was observed in patients infused with an A-ALC ≥ 0.5 x 109 lymphocytes/kg [OS: HR = 0.429, 95%CI, 0.128-0.828, p < 0.01; and PFS: HR = 0.456, 95% CI, 0.177-0.863, p < 0.01] and an A-NKC ≥ 0.09 x 109 cells/kg [OS: HR = 1.58e-3, 95% CI, 1.046e-6-0.179, p < 0.003; and PFS: HR= 1.58e-3, 95% CI, 7.81e-7-0.064, p < 0.003]. Furthermore, patients that maintained an ANKC ≥ 250 cells/µl at 3 months, 6 months, 9 months and 12 months post-APBHSCT also experienced superior OS (Figure 1A) and PFS (Figure 1B)[OS and PFS times in months were evaluated from infusion date of stem cells]. In the multivariate analysis a sustained ANKC ≥ 250 cells/µl was an independent predictor for OS (HR = 0.013, 95% CI, 0.001-0.063, p < 0.0001) and PFS (HR = 0.014, 95% CI, 0.001-0.067, p < 0.0001). This study is an extension of our Phase III clinical trial showing that sustained innate immunity by measuring the ANKC correlated with superior clinical outcomes; thus providing a platform to develop innate immunity immunotherapeutic strategists directing to improve clinical outcomes post-APBHSCT in NHL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autologous peripheral blood hematopoietic stem cell transplantation for patients with primary light chain amyloidosis: experience of 31 cases in a single center

目的探讨自体外周血造血干细胞移植（ASCT）治疗原发性轻链型淀粉样变性的疗效和安全性。方法回顾性分析2009年1月至2015年6月接受ASCT治疗的31例原发性轻链型淀粉样变性患者的临床资料、疗效、生存及转归。结果31例患者中男18例、女13例，中位年龄55(43~66）岁；20例患者为单器官受累；80.6%的患者为Mayo 1期；诊断至ASCT的中位时间为3(0.5~26）个月；粒细胞植入和血小板植入的中位时间分别为11(9~12) d和11(8~14) d；无移植相关死亡病例。在可评价疗效的27例患者中，总体血液学缓解率为85.2%（23例），其中完全缓解率和非常好的部分缓解率分别为63.0%（17例）和7.4%（2例），获得最佳血液学缓解的中位时间为4(1~21）个月。总体器官缓解率为59.2%，获得器官缓解的中位时间为8(3~18）个月。中位随访21个月，1例患者死亡，3例患者出现疾病进展，预计的3年无进展生存率和总生存率分别为92.8%和96.4%。结论ASCT对于早期原发性轻链型淀粉样变性患者是一种有效、安全的治疗手段。

Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization (G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF) on Engraftment and Sustained Graft Function: Comparison Across Cohorts with Similar CD34+ Cell Dose

AbstractAbstract 2255Effects of Method of Peripheral Blood Hematopoietic Stem Cell Mobilization, G-CSF, G-CSF + Plerixafor, or Cyclophosphamide + G/GM-CSF, on Engraftment and Sustained Graft Function: Comparison Across Cohorts With Similar CD34+ Cell Dose. Introduction:Autologous peripheral blood hematopoietic stem cell transplantation (AHSCT) is a key therapeutic modality in the management of multiple myeloma (MM) and lymphomas (Ly). The dose of CD34+ cells/kg in the mobilized peripheral blood product has long been regarded as the main determinant of neutrophil and platelet engraftment after AHSCT. Whether the method of hematopoietic stem cell mobilization, namely G-CSF alone (G), G-CSF + plerixafor (G+P) or cyclophosphamide +G/GM-CSF (Cy+G/GM) independently affects engraftment and graft function is unknown. Method:We used a database of AHSCT patients with MM or Ly to define 3 groups with different mobilization strategies (G, G+P, Cy+G/GM) but receiving similar CD34+ cell doses. Mobilization strategies had been determined by the standard practice at the time of the transplant (Cy + G/GM) or, more recently, by an algorithm factoring in the target CD34+ cell dose and the peripheral blood CD34+ count after 4 days of G-CSF mobilization (G and G+P). Imbalances in cell doses across the three groups were resolved by eliminating from the analysis patients with extremes of CD34+ doses (without investigator awareness of the engraftment endpoints) so all groups had similar averages and variation in CD34+ doses. The three groups were compared in terms of engraftment of neutrophils (defined as the first of 3 consecutive days with neutrophil count >500/mm3) and platelets (first of 3 consecutive days with platelet count >20,000/mm3 without transfusion). Comparisons of sustained graft function were based on total white blood cell count, absolute neutrophil count, and platelet count on or near day 100 after transplantation. All patients received G-CSF support after transplantation at 10 mcg/kg/day from day 7 until neutrophil engraftment. Results:The initial database contained 123 (70 MM and 53 Ly) patients undergoing transplantation in the three groups (26 G, 38 G+P and 59 Cy+G/GM). The average (+/− SD) cell doses (×106 CD34+/kg) were 4.56 +/−1.85, 5.3 +/−3.07 and 6.63+/−4.31 in G, G+P and Cy+G/GM respectively. After elimination of patients with extremes of CD34+ dose to correct imbalances, 99 patients remained in the analysis (26 G, 33 G+P and 40 Cy+G/GM), defining three groups with similar average and distribution of cell doses. Average cell doses and endpoints are shown in the table. There were no statistically significant differences in time to neutrophil engraftment across the three groups. Platelet engraftment was significantly slower in G+P (16.2 +/− 8.2 days) than in G (12.7 +/− 3.3) or Cy+GM (11.7 +/− 8.2; ANOVA P=0.03). There were no significant differences on day 100 total white blood cell count, absolute neutrophil count or platelet count among the three groups. Conclusions:Mobilization with G+P may lead to delayed platelet engraftment independently of CD34+ cell dose. Whether this effect is determined by plerixafor itself or by pre mobilization factors associated with plerixafor use remains to be determined. Day 100 graft function is not affected by mobilization strategy.Mobilization StrategiesPG (n=26)G+P (n=33)Cy+G/GM (n=40)CD 34+ cell dose (× 106/kg)4.57 +/− 1.854.83 +/− 1.944.67 +/− 1.03Neutrophil engraftment (days)12.9 +/− 2.614.2 +/− 4.012.9 +/− 3.60.23Platelet engraftment (days)12.7 +/− 3.316.2 +/− 8.211.7 +/− 8.20.03D100 white blood cell count(103/mm3)5.23 +/− 2.114.57 +/− 1.75.25 +/− 2.070.37D100 neutrophil count (103/mm3)3.17 +/− 1.492.6 +/− 1.053.27 +/− 1.870.23D100 platelet count (103/mm3)136 +/− 56154 +/− 66156 +/− 820.63 Disclosures:No relevant conflicts of interest to declare.

Absolute Lymphocyte Count Assessed During Routine Follow-up Is a Risk Factor for Relapse Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Patients with Diffuse Large B-Cell Lymphoma.

Abstract 4359Routine serial chimerism analysis after allogeneic stem cell transplantation (Allo-SCT) has been used as a risk factor for post-Allo-SCT cancer relapse. In non-Hodgkin lymphoma (NHL) patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APHSCT), a specific predictor during routine follow-up that could be used to ascertain risk for post-APHSCT relapse has not been identified. Thus, we set out to investigate if absolute lymphocyte count (ALC) measured at post APHSCT follow-up could serve as a marker of post-APHSCT NHL relapse. ALC was obtained at the time of confirmed relapse at follow-up and at last no evidence of relapse follow-up. From 1993 until 2005, 269 patients treated with APHSCT for diffuse large B-cell lymphoma (DLBCL), were included in this study. Patients at last follow-up with no relapse (N=137) had a higher ALC compared with those with confirmed relapsed at follow-up post-APHSCT (N= 132) [median ALC x 109/L of 1.66 (range: 0.13-3.69) vs 0.71 (range: 0.03-4.75), p <0.0001, respectively]. ALC at follow-up was a strong predictor for relapse with an area under the curve (AUC) = 0.86 (p<0.0001). An ALC of 1.0 × 109/L was identified as the optimal cut-off point. An ALC < 1.0 × 109/L at the time of confirmed relapse had a positive predictive value of 89% and a positive likelihood ratio of 8.4 to predict relapse post-APHSCT. Patients with an ALC ≥ 1.0 × 109/L (N = 147) had a cumulative incidence of relapse of 19% versus 92% for patients with an ALC < 1.0 × 109/L (N = 122) (p<0.0001) at follow-up post-APHSCT. This study suggests that ALC at follow-up can be used as a marker to assess risk of DLBCL relapse during routine follow-up after APHSCT. Disclosures:No relevant conflicts of interest to declare.

A clinical study of the hematopoietic stem cell transplantation in 112 patients with leukemia and other malignant diseases

One hundred and twelve patients received hematopoietic stem cell transplantation (HSCT), including 91 patients with acute leukemia, 12 patients with chronic myeloid leukemia, 7 patients with lymphoma and 2 patients with myeloma and neuroblastoma respectively. Among them, 14 patients were treated with unpurged autologous bone marrow transplantation (ABMT), 25 patients with purged autologous bone marrow transplantation (PABMT), 40 patients with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT), 24 patients with allogeneic bone marrow transplantation (Allo-BMT), 9 patients with fetal liver hematopoietic stem cell transplantation (FLHSCT). The three year disease free survival (DFS) rates in these five groups were 683%, 67.5%, 69.54%, 57.12% and 3333% respectively. The relapse rates were 30.76%, 26.80%, 20.8%, 13% and 62.5% respectively. In contrast, in the conventional chemotherapy group, the three year DFS rate and relapse rate were 738% and 76.4% respectively. These results indicated that the APBHSCT group had a quicker hematopoietic reconstitution with less complication of infection. All of these five transplantation groups had much higher three years disease free survival rates than that of the conventional chemotherapy group.