Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7039-7039
Author(s):  
Iman Aboudalle ◽  
Ronald Paranal ◽  
Shilpa Paul ◽  
Wen Li ◽  
Jing Ning ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Lymphoblastic Leukemia ◽  
Abnormal Uterine Bleeding ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem ◽  
Lh Receptor ◽  
Hematopoietic Recovery ◽  
Transfusion Requirements ◽  
Increased Risk ◽  
Leukemia Relapse

7039 Background: Treatment of acute leukemia with intensive chemotherapy (IC) leads to increased risk of infection and bleeding because of myelosuppression. Luteinizing hormone (LH) blockade was found to improve hematopoietic recovery in mice after radiation or chemotherapy through protection of the hematopoietic stem cells (HSCs) which express the LH receptor (Velardi et al, Nat Med 2018). We hypothesized that LH blockade improves hematopoietic recovery following IC in patients (pts) with leukemia. Methods: We assessed gene expression of the LH receptor (LHR) in lineage-specific normal and AML hematopoietic cells from a reference dataset (Corces et al, Nat Gen 2016). We conducted a retrospective analysis on pre-menopausal women with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received IC and Lupron, given for prevention or treatment of abnormal uterine bleeding. Results: LHR was greatest in HSCs, with little or no expression in mature subtypes within the hematopoietic hierarchy. Surprisingly, LHR was expressed on blasts. Since Lupron was more commonly given in younger pts, we performed propensity matching between the Lupron groups (AML N = 64; ALL N = 49) and control (Ctrl) groups (AML N = 128; ALL N = 98 pts). Baseline characteristics including blood counts were well balanced. Pts with AML who had received Lupron had a significantly higher increase in their platelet count following IC (13.8x109/L/year vs Ctrl; p = 0.02). Pts with ALL who had received Lupron had significantly higher increase in their absolute neutrophil count (0.37x109/L/year vs Ctrl; p = 0.02). AML pts in the Lupron group received significantly less blood transfusions vs Ctrl (mean: 23.9 vs 34.7 units; P = 0.002) and less platelet transfusions (mean: 24.4 vs 32.8 units; P = 0.06). There was no difference in event-free and overall survival between the groups in each leukemia cohort. Conclusions: Lupron use in leukemia pts receiving IC was associated with improved long-term blood count recovery. It was also associated with decreased transfusion requirements in AML. Despite expression of the LHR in blasts in addition to normal HSCs, there was no effect of LH blockade on rates of leukemia relapse or death.

scholarly journals Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Iman Abou Dalle ◽  
Ronald Paranal ◽  
Jabra Zarka ◽  
Shilpa Paul ◽  
Koji Sasaki ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Lymphoblastic Leukemia ◽  
Abnormal Uterine Bleeding ◽  
Intensive Chemotherapy ◽  
Additional Increase ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Increased Risk ◽  
Menopausal Women ◽  
And Control

Treatment of acute leukemia with intensive chemotherapy leads to an increased risk of myelosuppression. Luteinizing hormone (LH) blockade improves hematopoietic recovery in mice after radiation or chemotherapy, through protection of the hematopoietic stem cells which express the LH receptor. We hypothesized that LH blockade improves hematopoietic recovery following intensive chemotherapy in patients with leukemia. We conducted a retrospective analysis on pre-menopausal women with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received intensive chemotherapy and leuprolide given for abnormal uterine bleeding prevention or treatment. Given that leuprolide was more commonly administered in younger patients, we performed propensity score matching between the leuprolide (AML N=64; ALL N=49) and control groups (AML N=128; ALL N=98 patients). Patients with AML who received leuprolide had an additional increase of 13.8 x 109/L/year in their platelet count, and a 0.19 x 109/L/year increase in their lymphocyte count after chemotherapy compared to control (P=0.02; P=0.03 respectively). Those with ALL who received leuprolide had an additional increase of 0.37 x 109/L/year in their absolute neutrophil count (P=0.02). In AML, leuprolide was associated with higher long-term hemoglobin levels (P

scholarly journals Suppression of Luteinizing Hormone Enhances HSC Recovery after Hematopoietic Injuries

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 370-370
Author(s):  
Enrico Velardi ◽  
Jennifer Jia-ying Tsai ◽  
Kimon V. Argyropoulos ◽  
Shieh Jae-Hung ◽  
Sophie Lieberman ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Sex Steroids ◽  
Radiation Injury ◽  
Pool Size ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Lh Receptor ◽  
Pharmacological Inhibition ◽  
Hematopoietic Recovery

Abstract A tightly regulated network of intrinsic and extrinsic signaling pathways exists to preserve HSC pool size and function. This is particularly relevant during hematopoietic injuries when dormant HSCs transiently start to proliferate to replenish blood cells; as unbalanced HSC proliferation can lead to stem cell exhaustion, long-term myelosuppression and death. Although there has been growing interest in how circulating sex hormones influence HSC function (Nakada et al., 2014; Sanchez-Aguilera et al., 2014), this pathway remains poorly understood. Here we describe a heretofore unknown role for the upstream hormone regulator, luteinizing hormone (LH), in regulating HSC biology. We found that both human and mouse HSCs highly expressed the LH receptor, and its expression was decreased or nearly absent in downstream progenitors (Figure 1a). LH significantly promoted HSC colony forming potential in cobblestone area-forming cell and colony-forming cell assays that, together with expression of the receptor, suggested that LH increased HSC expansion in vitro by acting directly on the most primitive HSCs. To investigate whether LH levels could impact on HSC pool size during hematopoietic stress in vivo, we challenged mice using models that force HSCs out of their quiescent status, Poly I:C and sub-lethal dose of total body irradiation (SL-TBI, 550cGy). We found that ablation of LH production using a luteinizing hormone-releasing hormone-antagonist (LHRH-Ant) retained significantly more HSCs in G0 in both models (Figure 1b,c). Previous reports have shown that induction of HSC quiescence after high-dose irradiation correlates with increased hematopoietic recovery and enhanced mouse survival (Chen et al., 2008; Himburg et al., 2014; Johnson et al., 2010). Given its effectiveness in promoting HSC quiescence and the fact that LHRH-Ant are widely available and clinically approved, we hypothesized that LHRH-Ant could represent a rational non-cellular medical countermeasure for mitigating radiation injury and promoting hematopoietic regeneration when administered after hematopoietic insult. To test this hypothesis, we used a lethal TBI (L-TBI) dose of 840cGy that mediated lethality in more than 90% of B6 male mice. We found that pharmacological inhibition of LH using LHRH-Ant 24h after L-TBI spared the most primitive long term HSCs (Figure 1d) thus promoting hematopoietic recovery and mouse survival (Figure 1e). Consistent with our original hypothesis we also found a significantly higher proportion of Ki-67− quiescent HSCs in the LHRH-Ant-treated group with fewer proliferative HSCs compared to controls. Given the wide-ranging hormonal changes induced by LHRH suppression and the previously reported effects mediated by sex steroid ablation on hematopoietic stem/progenitor cell (HSPC) compartment (Khong et al., 2015), we next evaluated whether the LHRH-Ant effects on mouse survival after L-TBI were independent from the suppression of the downstream sex steroids. Administration of LHRH-Ant improved survival rates in surgically castrated mice following radiation injury, while surgical castration alone did not, indicating that the regenerative effects were independent from downstream sex steroids. To confirm whether the protective effects of LHRH-Ant treatment depended on suppression of LH, we administered the LH receptor agonist human chorionic gonadotropin (hCG) to LHRH-Ant treated mice that had been given L-TBI one-day prior. Consistent with our hypothesis, administration of hCG abrogated the beneficial effects of LHRH-Ant on survival after radiation injury. Taken together our studies showed that HSCs are a physiological target of LH, which promotes their proliferation. Furthermore, pharmacological inhibition of LH signaling using a single dose of an LHRH-Ant represents a rational and feasible approach to preserve the HSC pool after high dose radiation, thereby mitigating acute hematopoietic radiation syndrome. Disclosures Van Den Brink: Seres: Research Funding; Novartis: Consultancy; Regeneron: Consultancy; Flagship Ventures: Consultancy; Boehringer Ingelheim: Consultancy; Merck: Consultancy.

scholarly journals Ripk3 Signaling Regulates Hematopoietic Stem Cell Number and Function during Stress

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3714-3714
Author(s):  
Lei Zhang ◽  
Huacheng Luo ◽  
Jing Li ◽  
Hong-Min Ni ◽  
Mark Sellin ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Low Doses ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Leukemia Development ◽  
Serial Transplantation

Background: Among all tissues, bone marrow (BM) is the most sensitive tissue to ionizing radiation (IR)-induced acute tissue damage (ATD) and chronic long-term residual damage (LT-RD). BM failure and a significant reduction in blood cells (pancytopenia) often occurs within days after exposure to IR due to the massive death of proliferative hematopoietic progenitor cells (HPCs). However, due to their quiescent cell cycle status and reduced fidelity of DNA repair feature, many hematopoietic stem cells (HSCs) cannot fully eliminate such damage and enter senescence; this results in LT-RD. Abnormal dysplastic hematopoiesis is the most common LT-RD in most victims of IR, followed by an increased risk of leukemia/lymphoma development. Thus IR exposure is an established cause of BM failure and leukemia. A significant increase in the production of inflammatory cytokines is induced by IR which contributes to the pathogenesis of both ATD and LT-RD. Such inflammatory cytokines induce the activation of Ripk3-Mlkl-mediated necroptotic signaling in HSCs. However, the role of Ripk3-Mlkl signaling in IR-induced damage has not studied. Experimental procedures: The self-renewal capacity of HSCs among Ripk3-/-, Mlkl-/- and WT mice were examined and compared by serial transplantation assay. The phenotypes of ATD and LT-RD induced by different dosages of IR were compared among Ripk3-/-, Mlkl-/- and WT mice. The mechanism by which Ripk3 signaling prevents IR-induced leukemia development was studied. Results: Ripk3-Mlkl signaling is not required for hematopoiesis during homeostatic condition. However, during serial transplantation, inactivation of such signaling prevents stress-induced loss of HSCs. Interestingly, Ripk3 signaling also induces an Mlkl-independent ROS-p38-p16-mediated senescence in HSCs. Thus Ripk3-/- HSCs showed better competitive hematopoietic ability compared to Mlkl-/- and WT HSCs during serial transplantation. A sub-lethal dosage of IR (6Gy) induces Ripk3-dependent NF-κB activation and pro-survival gene expression in HSCs, which is necessary for the survival of damaged HSCs. After 6Gy IR, although DNA damage is repaired in most HSCs within 2 days, a proportion of HSCs in WT and Mlkl-/- mice fail to fully repair the damage and undergo p53-p21-dependent senescence. However such cells in Ripk3-/- mice die from apoptosis. Thus the remaining HSCs in Ripk3-/- mice should be functionally normal, while a proportion of the remaining HSCs in Mlkl-/- and WT mice remain damaged but senescent, all as demonstrated by competitive hematopoietic reconstitution assay. Multiple low-doses of IR (1.75Gy once week × 4) induce HSC exhaustion in WT mice but not in Ripk3-/- and Mlkl-/- mice. Interestingly, almost all Ripk3-/- mice develop acute lymphoblastic leukemia within 200 days after such low dose IR, while 45% of WT and 60% of Mlkl-/- mice develop thymomas within 360 days (see Figure). Mechanistically, such low-dose IR stimulates chronic inflammatory cytokine production. Such cytokines induce Ripk3-Mlkl-mediated necroptosis in response to HSC exhaustion observed in WT mice. These cytokines also induce Ripk3-ROS-p38-p16-mediated senescence in response to impaired HSC functioning observed in both WT and Mlkl-/- mice. In Ripk3-/- mice, due to the lack of both necroptotic and senescent signaling, mutant HSCs accumulate and leukemia development is accelerated. Conclusion: Ripk3 signaling plays distinct roles in HSCs in response to different doses of IR. High-dose IR induces Ripk3-dependent NF-κB/survival signaling, which is required for the survival of HSCs which fail to repair the damage. Thus temporal inhibition of Ripk3-NF-κB signaling might help to remove the damaged HSCs thus preventing the occurrence of LT-RD. However multiple low-doses of IR induces Ripk3 activation in HSCs which represses leukemia development by inducing both ROS-p38-p16-mediated senescence and Ripk3-Mlkl-mediated necroptosis. Induced activation of Mlkl-necroptosis might help to repress leukemia development by removing damaged HSCs. Disclosures No relevant conflicts of interest to declare.

scholarly journals HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1220-1226 ◽  
Author(s):  
Bronwen E. Shaw ◽  
Steven G.E. Marsh ◽  
Neema P. Mayor ◽  
Nigel H. Russell ◽  
J. Alejandro Madrigal
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Matched Pairs ◽  
Hematopoietic Stem ◽  
Tissue Typing ◽  
Increased Risk ◽  
Cell Transplants ◽  
Risk Of Disease

AbstractStudies in unrelated donor (UD) hematopoietic stem cell transplantations (HSCT) show an effect of the matching status of HLA-DPB1 on complications. We analyzed 423 UD-HSCT pairs. Most protocols included T-cell depletion (TCD). All pairs had high-resolution tissue typing performed for 6 HLA loci. Two hundred eighty-two pairs were matched at 10 of 10 alleles (29% were DPB1 matched). In 141 HLA-mismatched pairs, 28% were matched for DPB1. In the 10 of 10 matched pairs (n = 282), the 3-year probability of relapse was 61%. This was significantly higher in DPB1-matched pairs (74%) as compared with DPB1-mismatched pairs (56%) (log rank, P = .001). This finding persisted in multivariate analysis. In the group overall (n = 423), relapse was also significantly increased if DPB1 was matched (log rank; P < .001). These results were similar in chronic myeloid leukemia (CML; P < .001) and acute lymphoblastic leukemia (ALL; P = .013). In ALL, DPB1-matched pairs had a significantly worse overall survival (log rank; P = .025). Thus, in recipients of TCD UD-HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. It is possible that this effect is especially apparent following TCD transplantations and invites speculation about the function of DPB1 within the immune system.

scholarly journals Blinatumomab and Inotuzumab for the Treatment of Multiply Relapsed Acute Lymphoblastic Leukemia: A Real-Life Campus ALL Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3408-3408
Author(s):  
Mariarita Sciumè ◽  
Cristina Papayannidis ◽  
Antonio Curti ◽  
Antonella Vitale ◽  
Sabina Chiaretti ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lymphoblastic Leukemia ◽  
Real Life ◽  
Hematologic Toxicity ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Female Ratio ◽  
Immunotherapy Strategy ◽  
Blast Count

Abstract Blinatumomab (Blina) and inotuzumab (InO) have improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, many patients (pts) relapse after these treatments and little is known on their outcomes after recurrence and re-treatment with subsequent immunotherapy. We hereby describe the clinical characteristics and outcome of 71 pts with R/R B-ALL treated with both Blina and InO in any sequence - Blina/InO or InO/Blina - at different disease recurrences. At diagnosis, the median age was 34 years (15-64) and the male/female ratio was 1.6. Sixteen pts (22%) were Ph+ ALL, 3 (4%) were t(4;11)+ and 9 (13%) carried a complex karyotypes. ECOG PS was 0-1 in 66 pts (93%). At the time of the first immunotherapy, pts had received a median of 2 previous lines of treatment (1-8). All Ph- pts received intensive chemotherapy front-line; Ph+ pts received TKIs and steroids in 13 cases and intensive chemotherapy plus TKIs in 3 cases. Blina was the first salvage treatment (Blino/InO sequence) in 57 pts (80%) and InO (InO/Blina sequence) in 14 (20%). Twenty-seven pts (38%) had underwent a previous allogeneic hematopoietic stem cell transplantation (HSCT). At the start of Blina as first immunotherapy, the median bone marrow (BM) blast count was 40% (0-100%); at the start of InO as first immunotherapy, the median BM blast count was 64% (2-90%). An extramedullary involvement was present in 5 patients (9%) in the Blina/InO group and in 1 patients (7%) in the InO/Blina group. During immunotherapy, the median number of lumbar punctures was 2 (0-9). A median of 2 cycles were administered for both Blina (range 1-9) and Ino (range 1-4). In the Blina/InO group, after Blina a G3/4 toxicity occurred in 15 cases (26%): non-hematologic in 12 cases (21%), neurologic in 6 (8%). Infections occurred in 17 pts (30%). In the InO/Blina group, after InO a G3/4 toxicity occurred in 3 pts (21%), with extra-hematologic toxicity in 2 cases (14%, liver toxicity 1 case). Infections occurred in 4 cases (28%). In the Blina/InO group, after Blina 36 pts (63%) achieved a complete remission (CR), with a negative minimal residual disease (MRD) in 24 (42%) pts; after InO, a CR was re-achieved in 47 pts (82.4%), with 34 (59.6%) being MRD-. In the InO/Blina group, after InO a CR was reached in 13 cases (93%), with 6 pts (42.8%) being MRD-; after Blina, a CR was re-achieved in 6 pts (42.8%), with 3 (21.4%) being MRD-. This salvage immunotherapy strategy represented a bridge to alloHSCT for 26 pts (37%). From the first immunotherapy, in the Blina/InO group, the median overall survival (OS) was 19 months and after InO 6.3 months (OS in MRD- vs MRD+, p ns). Disease free survival (DFS) after Blina was 7.4 months (11.6 vs 2.7 months in MRD- vs MRD+ pts, p .03) and after InO it was 5.4 months (MRD- vs MRD+ pts, p ns). In the InO/Blina group, the median OS was 9.4 months and after Blina 4.6 months (7.5 vs 2.8 months in MRD- vs MRD+ pts, p .02). DFS after InO was 5.1 months (MRD- vs MRD+ pts, p ns) and after Blina it was 1.5 months (8.7 vs 2.5 gg in MRD- vs MRD+ pts, p .02). OS and DFS in MRD- pts after Blina was significantly better, both in the Blina/InO and the InO/Blina groups. With a median follow-up of 16.5 months from the start of immunotherapy and 33.8 months from initial diagnosis, 24 pts (34%) are alive and 16 (22%) are alive in CR. Four patients (6%) died in CR due to veno-occlusive disease during HSCT after InO treatment. Interestingly, OS and DFS from the first immunotherapy was better in pts with a previous alloHSCT (median survival 24.2 vs 13 months, p=.0135). AlloHSCT after second immunotherapy was associated with a better OS and DFS (OS 9.8 and DFS 7.2 months vs 7.8 and 4.4 months, p ns). Our real-life study in R/R B-cell ALL pts with multiple previous lines of treatment demonstrates the feasibility and efficacy of a sequential immunotherapy strategy in terms of MRD response, DFS and OS, and as a bridge to HSCT. SM and PC: equal contributors Disclosures Papayannidis: Janssen: Honoraria; Astellas: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Chiaretti: amgen: Consultancy; pfizer: Consultancy; novartis: Consultancy; Incyte: Consultancy. Forghieri: Jannsen: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Jazz: Honoraria. Bonifacio: Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Cerrano: Janssen: Honoraria; Insight: Honoraria; Jazz: Honoraria. Fracchiolla: Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy

2020 ◽  
Vol 11 ◽  
Author(s):  
Kai Wang ◽  
Yu Zhao ◽  
Xuan Wang ◽  
Bin Wang ◽  
Maoquan Qin ◽  
...  
Keyword(s):  
B Cell ◽  
Pulmonary Infection ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
B Cell Lymphoma ◽  
Primary Resistance ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Murine Antibody

BackgroundCD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10–20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.Case DescriptionA 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.ConclusionCD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.

scholarly journals Post-irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: a Retrospective Single-centre Cohort Analysis.

2020 ◽  
Author(s):  
Francesco Baldo ◽  
Roberto Simeone ◽  
Annalisa Marcuzzi ◽  
Rossella Vidimari ◽  
Francesca Ciriello ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Inclusion Criteria ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. Inclusion criteria were the following: recipient’s between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. Serum total amylase and pancreatic amylase were evaluated before, during and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. 57 patients were treated with fractionated TBI and 21 with a single dose regimen. Overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66-0.86; P < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. TA showed high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77 – 0.93; P < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines such as TNF-α, IL-6 and RANTES (P < 0.001).Conclusions: This study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.

scholarly journals Clinical Outcomes of COVID-19 Infection Among Children with Cancer: A Single-Center Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3366-3366
Author(s):  
Esra Akkoyun ◽  
Jesus Sotelo ◽  
Giselle Cherry ◽  
Maria Bisceglia ◽  
Tamra Slone ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Invasive Mechanical Ventilation ◽  
Neutropenic Fever ◽  
Myelogenous Leukemia ◽  
Critically Ill Children ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Underlying Malignancy ◽  
Increased Risk ◽  
History Of

Abstract Background Outcomes of COVID-19 infection among children with underlying malignancy remain unclear, with limited data available to date. Here we report clinical characteristics and outcomes following COVID-19 infection among children with underlying malignancy or a history of hematopoietic stem cell transplant (HSCT) during the first year of the global COVID-19 pandemic, in Dallas, TX. Methods: We retrospectively reviewed children with a history of malignancy or prior HSCT and positive SARS-CoV-2 polymerase chain reaction (PCR) result between March 1, 2020 - March 31, 2021. Demographic, clinical, and outcome data were reviewed, and analyzed according to underlying condition and disease severity. Results: Forty-six patients with underlying malignancy or HSCT met inclusion criteria. Median age was 9 years, with twenty (43%) female, and twenty-seven (59%) of Hispanic ethnicity. Underlying conditions included Acute Lymphoblastic Leukemia (67%), Acute Myelogenous Leukemia (9%), HSCT (11%), sarcoma (9%), solid tumors (9%), and Hodgkin's lymphoma (2%). Fifteen subjects (33%) were asymptomatic, with twenty-four children (52%) classified as having mild, five (11%) with severe, and two (4%) with critical COVID-19 disease. The most common symptoms at presentation were fever (46%), cough (39%), and gastroenteritis (19%). Thirty-four children (74%) were hospitalized, with seven (15%) requiring intensive care unit (ICU) care. 17% of patients were admitted for treatment of COVID-19 alone, with other indications including neutropenic fever, relapse, and chemotherapy. Six (13%) patients required non-invasive ventilation, and two patients (4%) required invasive mechanical ventilation. Median length of stay was 9 days (IQR 4.5-24.5), with median ICU stay of 3.5 days (IQR 2-26.7). Seven children (15%) received COVID-19 targeted therapy including steroids, remdesivir or convalescent plasma. Among severe and critically ill children, six (86%) had underlying hematologic malignancies (5 HR ALL, 1 AML), and two (28%) a prior history of HSCT. Two children (4%) died. Thirty-six patients (78%) achieved documented clearance of SARS-CoV-2 by PCR, at median of 43.5 days (IQR 28.7-65.2). Conclusion: Among children with underlying malignancy or a history of HSCT, COVID-19 results in a spectrum of illness ranging from asymptomatic disease to death. Rates of hospitalization are high compared to the general pediatric population, and illness may be complicated by additional factors including co-infection, neutropenic fever, relapse of malignancy and need for chemotherapy. Children with hematologic malignancy or a history of HSCT may be at increased risk for severe disease. Additional studies are urgently needed to elucidate risk factors for severe/critical COVID-19 disease among children with underlying malignancy. Disclosures No relevant conflicts of interest to declare.

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