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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1836-1836
Author(s):  
Luis F. Porrata ◽  
David J. Inwards ◽  
Stephen M. Ansell ◽  
Ivana N. Micallef ◽  
Patrick B. Johnston ◽  
...  

Abstract 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. Figure 1 Figure 1. Disclosures Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4348-4348
Author(s):  
Meerim Park ◽  
Kyung Nam Koh ◽  
Keun Wook Bae ◽  
Mee Jeong Lee ◽  
Ho Joon Im ◽  
...  

Abstract Abstract 4348 Background Hematopoietic stem cell transplantation (HSCT) from matched sibling donor is the standard first-line treatment for children with severe aplastic anemia (SAA). However, the management of SAA lacking a suitable donor remains a great challenge. For those children, HSCT using unrelated donor or mismatched related donor could be a therapeutic alternative. The purpose of this study is to evaluate the outcome in children with SAA who received HSCT from donors other than matched sibling. Patients and Method Between March 2003 and July 2009, 17 patients received HSCT from alternative donors (AD) at Asan Medical Center. We reviewed their medical records and analyzed their transplant-related parameters and outcome. Results Of a total of 17 patients, 11 were male and the median age at HSCT was 9.0 years, ranging from 3.0 to 16.7 years. Four patients had Fanconi anemia and 13 had acquired SAA including 2 who developed SAA after liver transplantation. Donors included unrelated bone marrow (U-BM) in 5, unrelated peripheral blood (U-PB) in 6, unrelated cord blood (U-CB) in 2 and related haploidentical peripheral blood (H-PB) in 4. Of 17 patients, 15 (88%) achieved sustained engraftment. Of 15 with engraftment, only 1 patient who received HSCT from U-CB died of severe GI GVHD and the other 14 patients remain on stable normal counts without transfusion support. All 2 patients (1 U-BM, 1 H-PB) who failed to engraft were dead despite DLI or 2nd HSCT. With a median follow-up of 31.9 months, the Kaplan-Meier estimated overall survival at 2 years was 76.6%. Conclusion In children with SAA, HSCT from AD including haploidentical family donor could be considered as a treatment option if the patients have no matched sibling donor. Given the limitation of this study such as small number of patients and short follow-up period, further trial will be necessary. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3963-3963
Author(s):  
Qamar Iqbal ◽  
Moazzam Shahzad ◽  
Ezza Tariq ◽  
Laila Hashim ◽  
Abdul Basit ◽  
...  

Abstract Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by the hyper-stimulation of the immune system. HLH has a poor prognosis with up to a 100% mortality without an adequate therapy. Contrary to primary HLH, an efficient management approach has yet to be established for secondary HLH in adults. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of hematopoietic stem cell transplantation (HSCT) in this context. Methods Following the preferred reporting items for systemic reviews and Mata-analysis (PRISMA) guidelines, a comprehensive literature search was performed on 4 databases (PubMed, Cochrane Register of Controlled Trials, Embase and Clinicaltrials.gov) using MeSH terms and keywords for "Lymphohistiocytosis, Hemophagocytic" AND "Hematopoietic stem cell transplantation" AND "Therapeutics" AND "Treatment Outcome" from the date of inception to June 2021. Our search produced 2346 results and duplicates were removed. After excluding irrelevant and review articles during primary and secondary screening, seven original studies reporting HSCT as the treatment for secondary HLH in pediatric and adult patient population were included. The methodological quality of the included studies was evaluated using NIH quality assessment tool. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 136 patients from 7 studies were included. The median age of the patients was 32 (0.5-77) years and 57.4% (62/108) were males as reported by 4 studies. (Table 1) Allogeneic HSCT was used as a treatment modality for 100% (n=136) of the patients. The median time from diagnosis to HSCT was 4.9 (0.1-24) months as reported by 3 studies and median follow-up time was 22 (3-192) months as reported by 4 studies. The pooled overall response rate (ORR) after HSCT was 80% (95% CI 0.66-0.91, I 2 =21%, n=59) with pooled complete response (CR) of 54.5% (95% CI 0.19-0.87, I 2 =86%, n=59) and pooled partial response (PR) of 22.4% (95% CI 0.04-47, I 2 =72%, n=59). At a median follow-up of 30 (3-120) months, the pooled overall survival (OS) was 78.8% (95% CI 0.67-0.89, I 2 =41%, n=136). The pooled relapse rate (RR) was 12.2% (95 CI 0.045-0.22, I 2 =0%, n=61). The pooled incidence of acute graft versus host disease (GVHD) grade I/II and grade III/IV was 37.5% (95% CI 0.24-0.51, I 2 =0%, n=48) and 19.8% (95% CI 0.09-0.32, I 2 =0%, n=50) respectively, while pooled incidence of chronic GVHD was 26% (95% CI 0.13-0.41, I 2 =25%, n=50). Conclusion: HSCT shows excellent response rates and survival in patients with secondary HLH with an acceptable safety profile and should be considered. However, it is imperative that large prospective studies should be done to consolidate these findings. Figure 1 Figure 1. Disclosures McGuirk: Novartis: Research Funding; Gamida Cell: Research Funding; Astelllas Pharma: Research Funding; EcoR1 Capital: Consultancy; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4973-4973
Author(s):  
Elias H. Atta ◽  
Cláudia J.P.B. Coelho ◽  
Silvia M.P. Sarcinelli ◽  
Cláudia A. Máximo ◽  
Alexandre M. Azevedo ◽  
...  

Abstract Background: Early absolute lymphocyte count (ALC) recovery after autologous peripheral hematopoietic stem cell transplantation (ASCT) has been reported as an independent prognostic factor for overall survival and progression-free survival for patients with hematological and non-hematological cancers. Early immune reconstitution appears to have a protective effect against residual disease after ASCT. End points: Assessment of factors impacting on early ALC recovery after ASCT. Methods: Retrospective analysis of the ASCT procedures done between 2000 and 2007 in Hemorio. Early lymphocyte recovery (ELR) was defined as an ALC ≥500/μL at day 12 after ASCT. Results: A total of 53 of 66 consecutive ASCT (80,3%) were eligible for this study. Of the 53 ASCT, 9 were for lymphoma, 22 for multiple myeloma and 22 for acute myelogenous leukemia. Median age of the group was 34 years (range: 13–65). All patients except one were mobilized with chemotherapy plus granulocyte colony-stimulating factor (G-CSF). ELR was observed in 41% of the patients. Univariate analysis identified an association between the following factors and ELR: median pre-mobilization ALC (1920 vs 1060 lymphocytes/μL; p=0.003), pre-collection ALC (1637 vs 747 lymphocytes/μL; p<0.001), dose of leukocytes infused (1.21 x 109 vs 0.65 x 109 leukocytes/kg; p=0.002), dose of lymphocytes infused (0.26 x 109 vs 0.10 x 109 lymphocytes/kg; p<0.001), dose of CD4+ lymphocytes infused (0.075 x 109 vs 0.034 x 109 CD4+ lymphocytes/kg; p<0.001) and dose of CD8+ lymphocytes infused (0.11 x 109 vs 0.03 x 109 CD8+ lymphocytes/kg; p<0.001) were all higher in the ELR group. Patient diagnosis, number of previous cycles of chemotherapy and number of CD34+ cells collected were not correlated with ELR. Forward stepwise regression identified the pre-mobilization ALC and the number of lymphocytes in the autograft as factors related to ELR (p=0.013 and p<0.001; respectively). Multivariate analysis demonstrated that the lymphocyte dose in the graft can be predicted by the pre-collection ALC and the number of aphereses carried out (p<0.001 for both). Median pre-mobilization ALC was higher than pre-collection ALC (1335 vs 975 lymphocytes/μL respectively; p=0.013). This difference was most significant in the group of patients without ELR (1060 vs 747 lymphocytes/μL respectively; p=0.004). Among patients with ELR, the difference was not significant (1920 vs 1637 lymphocytes/μL respectively; p=0.53). Conclusions: These results indicate that ELR after ASCT depends on the pre-mobilization ALC and the lymphocyte dose in the autograft. The number of aphereses performed for stem cell collection and the pre-collection ALC predict the number of lymphocytes collected. Stem cell mobilization with chemotherapy and G-CSF significantly reduces the ALC at the time of collection, specially in patients with lower ALC at the time of the mobilization. Strategies to improve immunologic recovery may have an impact on the results of ASCT. Figure Figure


2014 ◽  
Vol 6 (1) ◽  
pp. e2014047 ◽  
Author(s):  
Grzegorz Helbig ◽  
Malgorzata Krawczyk-Kulis ◽  
Malgorzata Kopera ◽  
Krystyna Jagoda ◽  
Patrycja Rzepka ◽  
...  

Objective. To evaluate the efficacy and toxicity of autologous hematopoietic stem cell transplantation (AHSCT) for high-risk acute lymphoblastic leukemia (ALL). Material and methods. Overall, 128 high-risk ALL patients at a median age of 26 years (range 18-56 years) at diagnosis received AHSCT between 1991-2008. Induction treatment was anthracycline-based in all patients. Conditioning regimen consisted of CAV (cyclophosphamide, cytarabine, etoposide) in 125 patients whereas 3 subjects received cyclophosphamide and TBI (total body irridation). Bone marrow was stored for 72 hours in 4oC and re-infused 24 hours after conditioning completion. Bone marrow was a source of stem cells in 119 patients, peripheral blood in 2 and 7 subjects received both bone marrow and peripheral blood. Results. With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3 years), the probability of leukemia-free survival (LFS) for the whole group at 10 years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after AHSCT was 3.2%.. There was a strong tendency for better LFS for MRD-negative patients if compared with patients who had positive or unknown MRD status at AHSCT (32% vs 23% and 25%, respectively; p=0.06). There was no difference in LFS between B- and T-lineage ALL as well as between patients transplanted in first complete remission (CR1) and CR2. LFS at 10 years for patients with detectable BCR-ABL at transplant was 20% and this was comparable with subjects with negative and missing BCR-ABL status (26% and 28%; p=0.97). Conclusions. The results of AHSCT for high-risk ALL remains unsatisfactory with low probability of long-term LFS.


2009 ◽  
Vol 84 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Elias Hallack Atta ◽  
Alexandre Mello de Azevedo ◽  
Angelo Maiolino ◽  
Cláudia Júlia Bruzzi Porto Coelho ◽  
Silvia Maria Patiño Sarcinelli ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 892-892 ◽  
Author(s):  
Luis F. Porrata ◽  
Dennis A. Gastineau ◽  
Alvaro Pineda ◽  
Jeffrey L. Winters ◽  
S. Breanndan Moore ◽  
...  

Abstract Peripheral blood infused total autograft absolute lymphocyte count (A-ALC) correlates with day 15 absolute lymphocyte count and is an independent prognostic factor for survival after autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL). Factors to enhance A-ALC collections are not well defined. We hypothesize that the number of peripheral blood apheresis collections (PBAC) directly correlates with A-ALC. 190 consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1993 and 2001 were analyzed. The primary end point of the study was to assess the correlation between the number of PBAC and A-ALC. The secondary end point was to determine if the number of PBAC affected survival post-ASCT. Of the 190 patients, 18 patients underwent 1 PBAC, 23 patients 2 PBAC, 50 patients 3 PBAC, 37 patients 4 PBAC, 50 patients 5 PBAC, and 12 patients had ≥ 6 PBAC. There was no association between the number of PBAC and the number of CD34+ stem cells collected (p= 0.25). A strong association between number of PBAC and A-ALC (Kruskall Wallis test, p <0.0001)(Figure 1) was identified. Using a cut-off of 4 PBAC, superior overall survival (OS) and progression-free survival (PFS) were observed for patients that underwent 4 PBAC or more compared to patients that underwent less than 4 PBAC (86 months vs 18 months, p <0.0001; 76 months vs 10 months, p <0.0001, respectively). Multivariate analysis demonstrated PBAC ≥ 4 is an independent prognostic factor for OS (RR = 0.654, 95%CI: 0.529–0.804, p< 0.0001) and for PFS (RR = 0.682, 95%CI: 0.561–0.826, p< 0.0001) when compared with other significant factors including performance status, lactate dehydrogenase and extra nodal disease. These data suggest that increasing the number of PBAC beyond the minimum number required to meet CD34+ collection targets may result in improved overall and progression-free survival mediated by an increase in autograft absolute lymphocyte count.


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