Contributions
Abstract: EP741
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Collection targets for autologous hematopoietic stem and progenitor cell (HSPC) gene therapy (GT) should ideally account for the cell manipulation process and for unmanipulated backup storage. Therefore higher amounts of HSPCs in comparison to conventional autologous and allogenic HSPC transplantation harvests are required.
While pediatric donors have historically undergone bone marrow (BM) harvest, HSPC mobilization and apheresis may be safer and more suitable for the purpose of autologous GT.
Aims
To analyze the safety and collection yields of peripheral blood stem and progenitor cells (PBSCs) collection in pediatric candidates for GT.
Methods
We retrospectively analyzed the mobilization and apheresis procedures of all consecutive pediatric (<18 years) patients treated at IRCCS Ospedale San Raffaele (OSR) between April 1st 2010 and March 31st 2020, candidate to GT for for adenosine deaminase deficiency (ADA-SCID), b-thalassemia, metachromatic leukodystrophy (MLD), mucopolysaccharidosis 1 Hurler (MPSIH), or Wiskott-Aldrich syndrome (WAS).
Results
We included 45 consecutive patients (ADA-SCID = 4, b-thalassemia = 7, MLD = 10, MPSIH = 8, WAS = 16), who underwent mobilization with lenograstim, with (n=41) or without (n = 4) plerixafor, and 1-3 cycles of leukapheresis. Median weight was 15.8 kg (range 7-54.1); median age was 3.7 years (0.4-14.4). Forty patients were enrolled upfront to mobilization and leukapheresis, for collection of both the drug product (DP) starting material and an unmanipulated backup, while five for potential or actual limitations of BM harvest. HSPCs were used as a starting material for the manufacture of the DP (n = 2), cryopreserved for backup (n = 2), or both (n = 41). We recorded 108 adverse events within 14 days following the last apheresis, mostly of grade 1-2 (87%).
Minimum collection targets were usually 7-13 x106 CD34+/kg. Overall, patients collected a median of 37.0 x106 CD34+ cells/kg (range of 3.3-63.8 x106); male gender, underlying disease (b-thalassemia) and lower drug dose were found to be positive predictors of yield. Only three patients among those that underwent mobilization upfront (n = 40) required an additional HSPC collection.
42/43 backups were >2 x 106 CD34+ cells/kg; 41/42 patients received a drug product dose in the reference infusion range (from 4 to 30.9 x106 CD34+ cells/kg), and all patients that received the drug product engrafted.
As compared to our historical cohort of BM harvests, mobilization and leukapheresis allowed the collection of a higher number of cells in a short period of time. Shorter duration of anesthesia – required to place a central venous catheter – lower fluctuations in intravascular volume and reduced pain are additional advantages of PBSC collection.
Conclusion
Mobilization and leukapheresis allow the collection of a large number of HSPCs, even in pediatric donors of low weight, with a favorable safety profile, satisfying GT requirements. Beyond GT, the collection of large number of HSPCs by mobilization and leukapheresis may overcome significant weight discrepancies between a pediatric donor and a familial HSCT recipient, and prospectively allow to implement HSPC selection strategies.
Keyword(s): Gene therapy, Leukapheresis, Mobilization, Pediatric
Abstract: EP741
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Collection targets for autologous hematopoietic stem and progenitor cell (HSPC) gene therapy (GT) should ideally account for the cell manipulation process and for unmanipulated backup storage. Therefore higher amounts of HSPCs in comparison to conventional autologous and allogenic HSPC transplantation harvests are required.
While pediatric donors have historically undergone bone marrow (BM) harvest, HSPC mobilization and apheresis may be safer and more suitable for the purpose of autologous GT.
Aims
To analyze the safety and collection yields of peripheral blood stem and progenitor cells (PBSCs) collection in pediatric candidates for GT.
Methods
We retrospectively analyzed the mobilization and apheresis procedures of all consecutive pediatric (<18 years) patients treated at IRCCS Ospedale San Raffaele (OSR) between April 1st 2010 and March 31st 2020, candidate to GT for for adenosine deaminase deficiency (ADA-SCID), b-thalassemia, metachromatic leukodystrophy (MLD), mucopolysaccharidosis 1 Hurler (MPSIH), or Wiskott-Aldrich syndrome (WAS).
Results
We included 45 consecutive patients (ADA-SCID = 4, b-thalassemia = 7, MLD = 10, MPSIH = 8, WAS = 16), who underwent mobilization with lenograstim, with (n=41) or without (n = 4) plerixafor, and 1-3 cycles of leukapheresis. Median weight was 15.8 kg (range 7-54.1); median age was 3.7 years (0.4-14.4). Forty patients were enrolled upfront to mobilization and leukapheresis, for collection of both the drug product (DP) starting material and an unmanipulated backup, while five for potential or actual limitations of BM harvest. HSPCs were used as a starting material for the manufacture of the DP (n = 2), cryopreserved for backup (n = 2), or both (n = 41). We recorded 108 adverse events within 14 days following the last apheresis, mostly of grade 1-2 (87%).
Minimum collection targets were usually 7-13 x106 CD34+/kg. Overall, patients collected a median of 37.0 x106 CD34+ cells/kg (range of 3.3-63.8 x106); male gender, underlying disease (b-thalassemia) and lower drug dose were found to be positive predictors of yield. Only three patients among those that underwent mobilization upfront (n = 40) required an additional HSPC collection.
42/43 backups were >2 x 106 CD34+ cells/kg; 41/42 patients received a drug product dose in the reference infusion range (from 4 to 30.9 x106 CD34+ cells/kg), and all patients that received the drug product engrafted.
As compared to our historical cohort of BM harvests, mobilization and leukapheresis allowed the collection of a higher number of cells in a short period of time. Shorter duration of anesthesia – required to place a central venous catheter – lower fluctuations in intravascular volume and reduced pain are additional advantages of PBSC collection.
Conclusion
Mobilization and leukapheresis allow the collection of a large number of HSPCs, even in pediatric donors of low weight, with a favorable safety profile, satisfying GT requirements. Beyond GT, the collection of large number of HSPCs by mobilization and leukapheresis may overcome significant weight discrepancies between a pediatric donor and a familial HSCT recipient, and prospectively allow to implement HSPC selection strategies.
Keyword(s): Gene therapy, Leukapheresis, Mobilization, Pediatric