scholarly journals Longitudinal Analysis of the Effect of Hematopoietic Cell Transplantation on Ocular Disease in Children with Mucopolysaccharidosis I Shows Ongoing Disease Progression

2019 ◽  
Vol 25 (3) ◽  
pp. S41-S42
Author(s):  
Brigitte T.A. van den Broek ◽  
Jens Achterberg ◽  
Jaap-Jan Boelens ◽  
Michelle van Egmond-Ebbeling ◽  
Peter M. van Hasselt
Keyword(s):  
Disease Progression ◽  
Cell Transplantation ◽  
Longitudinal Analysis ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Ocular Disease ◽  
Mucopolysaccharidosis I

scholarly journals Longitudinal Analysis of Ocular Disease in Children with Mucopolysaccharidosis I after Hematopoietic Cell Transplantation

2020 ◽  
Vol 26 (5) ◽  
pp. 928-935 ◽  
Author(s):  
Brigitte T.A. van den Broek ◽  
Michelle B. van Egmond-Ebbeling ◽  
Jens A. Achterberg ◽  
Jaap Jan Boelens ◽  
Isa C. Vlessert ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Longitudinal Analysis ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Ocular Disease ◽  
Mucopolysaccharidosis I

scholarly journals Pembrolizumab for the Treatment of Disease Relapse Following Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3415-3415 ◽  
Author(s):  
Justin Kline ◽  
Hongtao Liu ◽  
Tallarico Michael ◽  
Andrew S Artz ◽  
James Godfrey ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Myeloid Sarcoma ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Disease Relapse ◽  
Grade 3

Abstract Background: Disease relapse remains the primary cause of mortality following allogeneic hematopoietic cell transplantation (alloHCT). One important mechanism of disease relapse in this setting is failure of the graft-versus-tumor (GvT) effect, and the PD-1/PD-L1 axis may diminish GvT after alloSCT. We hypothesized that PD-1/PD-L1 interactions prevent donor-derived T cells from eliminating malignant cells expressing minor histocompatibility antigens, and that blocking PD-1/PD-L1 interactions with the anti-PD-1 antibody, pembrolizumab (pem), might restore GvT and induce clinical responses in patients (pts) with relapsed hematologic malignancies following alloHCT. However, PD-1 blockade therapy has been associated with severe graft-versus-host disease (GVHD) in murine models, and GVHD has been reported in humans treated with anti-PD-1 therapy after alloHCT. Thus, we developed a prospective clinical study to test the tolerability and preliminary efficacy of pembrolizumab in patients with relapsed leukemia/lymphoma after alloSCT. Methods: Pts with AML, MDS, or B cell lymphomas with biopsy-proven recurrence after alloSCT were eligible, as long as no active acute GVHD > grade 1 or chronic GVHD was present. Pts were treated with pem 200 mg IV q3 weeks for up to 2 years, provided that neither intolerable side-effects nor disease progression occurred. Pem could be delayed for treatment-limiting toxicities (TLT), defined as immune-related adverse events (irAEs) not meeting criteria for a dose-limiting toxicity (DLT). DLT was defined as the development of grade 3 or 4 acute GVHD/irAE, any unexpected grade > 2 toxicity related to pem, or development of > grade 2 vital organ dysfunction secondary to an irAE within 90 days of pem initiation. A two-stage mini-max design was chosen, with an early stopping rule for DLT after the first 11 patients were enrolled. Results: 11 pts (7 male, 4 female), mean age 49.5 yrs (range, 27-62 yrs) have been enrolled. 8 pts had AML and 3 had lymphoma (DLBCL - 2, cHL - 1). 6 pts had matched-related donors (MRD) and 5 pts had haploidentical/umbilical cord blood (haplo-cord) donors. Pts with MRD were conditioned with fludarabine, melphalan, and alemtuzumab, or fludarabine and busulfan. Pts with haplo-cord donors were conditioned with fludarabine, melphalan, and ATG. 5 pts had prior acute GVHD. Pts relapsed following alloHCT at a median of 453 days (range, 101-1021 days). A median of 2 cycles of pembrolizumab (range, 1-8) was administered. 3 pts are receiving ongoing treatment. 3 pts experienced a DLT due to an irAE (grade 3-4 pneumonitis 2 pts; grade 3 hyperthyroidism 1 pt), all of which occurred after 1-2 cycles of pem, and resolved after pem discontinuation and corticosteroid treatment. 1 pt experienced a TLT (grade 2 rash), but resumed pem treatment. Among all pts, irAEs of any grade occurred in 7 pts. 7 pts were evaluable for response. 3 pts (2 AML, 1 DLBCL) experienced progressive disease (PD), 2 pts (AML) had stable disease (SD), and 2 pts achieved CR (DLBCL, cHL). 1 pt with AML (myeloid sarcoma) in whom pem was discontinued for PD by PET/CT imaging had a concurrent tumor biopsy that revealed marked T cell infiltration and PD-L1 expression on a significant fraction of malignant myeloid cells, suggestive of possible inflammatory "pseudo-progression". 1 pt in CR developed therapy-related AML unrelated to pem. Notably, both patients with CR following pem had PD-L1 gene-amplified lymphomas by FISH, and diffuse PD-L1 protein expression on pre-treatment biopsies. Currently, 4 pts have died, all due to disease progression, and 7 are alive. A total of 26 patients are expected to be enrolled. Conclusions: Treatment with pem in the post-alloHCT disease relapse setting is feasible, but can induce early and severe irAEs, requiring vigilant monitoring. To date, objective responses were seen in 2/3 lymphoma patients treated with pem. In AML, pem may be less effective, where a best response of SD was observed in 2 pts, and possible "pseudo-progression" in a patient with myeloid sarcoma. This study continues to accrue pts, and correlative analyses are underway. To our knowledge, these are the first prospective data of PD-1 blockade therapy in the post-alloHCT setting. Disclosures Kline: iTeos: Research Funding; Merck: Honoraria, Research Funding. Liu:BMS: Research Funding. Curran:Merck: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Smith:BMS: Consultancy; Portola: Honoraria. Bishop:Juneau Therapeutics: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; United Healthcare: Employment; Novartis Pharmaceuticals Corporation: Speakers Bureau.

Effect of Interventions for Relapse or Progression Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience of 93 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1648-1648
Author(s):  
Saiko Kurosawa ◽  
Takahiro Fukuda ◽  
Shin-ichiro Mori ◽  
Sung-Won Kim ◽  
Shigeo Fuji ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Systemic Relapse ◽  
Reduced Intensity

Abstract Background: Relapse/progression after allogeneic hematopoietic cell transplantation (HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome in a modern transplant setting was overviewed to improve decision-making. Patients and immediate therapy: Between 2000 and 2006, 294 patients with leukemia/MDS received allogeneic HCT after myeloablative (n=145) or reduced-intensity (n=149) conditioning. Among them, 93 patients (32%) either relapsed or showed disease progression; the relapse rate was 40% for AML (57/144 patients), 18% for MDS (13/72), 14% for CML (5/35), and 42% for ALL (18/43). The median overall survival (OS) after relapse or progression was 167 days (range; 5 to 1456 days). Twenty-eight patients (30%) were elected to receive no interventions with curative intent other than withdrawal of immunosuppressant, less-intensive chemotherapy or DLI, mostly due to comorbidities or refractoriness of the disease, and all but 3 patients died with disease progression at a median of 61 days. Two other patients underwent immediate HCT without intervention due to graft failure. Among the remaining 63 patients (68%) who received therapeutic interventions including re-induction chemotherapy with or without DLI, 26 (41%) achieved subsequent complete remission (CR). Salvage transplantation: Forty-five patients (15 in CR and 30 in non-CR) did not undergo a second HCT due to various reasons including progressive disease (n=28), infection (n=6), GVHD (n=3), refusal (n=3), and rather stable disease (n=5). Overall, 20 patients underwent salvage HCT using myeloablative (n=8) or reduced-intensity (n=12) conditioning: 11 in CR and 9 in non-CR. The incidence of TRM after the second HCT was not remarkable (5%). The probability of achieving CR after the second HCT was 75%, compared to 35% after other interventions (p=0.001), and the 1-year OS after relapse was significantly better in patients with the second HCT than that in others (58% vs 14%, p<0.0001), but these favorable outcomes may simply reflect the patient-selection bias. The 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after a second HCT. Currently, 15 of the 93 patients (16%) are alive with a median follow-up of 346 days (range; 33 to 1456 days), and 10 of these patients are still in CR. Notably, 5 patients are alive in CR without a second HCT: 3 suffered from central nervous system relapse without systemic relapse and received localized therapy alone (follow-up; 494 to 1456 days), and the remaining 2 have had a rather short follow-up after DLI. Multivariate analysis showed that re-induction chemotherapy, CR after intervention, a second HCT, and a longer time to post-transplantation relapse (≥100 days) were associated with improved OS after relapse. Conclusion: For patients with chemosensitive systemic relapse, a second allogeneic HCT may improve survival and could be considered as an effective therapeutic option. Figure Figure

scholarly journals Human Metapneumovirus Infections Following Hematopoietic Cell Transplantation: Factors Associated With Disease Progression

2016 ◽  
Vol 63 (2) ◽  
pp. 178-185 ◽  
Author(s):  
Sachiko Seo ◽  
Ted A. Gooley ◽  
Jane M. Kuypers ◽  
Zachary Stednick ◽  
Keith R. Jerome ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Human Metapneumovirus ◽  
Hematopoietic Cell ◽  
Factors Associated

Efficacy of keratinocyte growth factor in prevention of oral mucositis in children undergoing allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 51 (3) ◽  
pp. 172-178
Author(s):  
Natalia Bartoszewicz ◽  
Krzysztof Czyżewski ◽  
Robert Dębski ◽  
Anna Krenska ◽  
Ewa Demidowicz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Transplantation ◽  
Oral Mucositis ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Course ◽  
Keratinocyte Growth Factor ◽  
Supportive Therapy ◽  
Primary Objective ◽  
Hematopoietic Cell ◽  
Unrelated Donor

AbstractIntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

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