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113 TNC/Kg and CD34+/Kg Cell Dose Impact on Patient Engraftment after Allogeneic Transplant with Conventional Bone Marrow; Better Predictability of Graft Content Needed

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Improving Outcomes by Reducing Transplant-Related Complications
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality)
Saturday, December 9, 2023: 10:30 AM

Eric Davis, MPH, CHTC1,2*, Elise Feuer3*, Candice Rapoport2*, Stephanie Lobaugh4*, Sean M. Devlin, PhD5*, Anne Archer1,2*, Stephanie Chinapen2*, Jacob Federman6*, Amanda Kelly2*, Elizabeth Klein1*, Melissa Nhaissi6*, Deborah Wells6*, Juliet N Barker, MBBS6,7, Esperanza B. Papadopoulos, MD6,8, Andromachi Scaradavou, MD1,9, Jaap Jan Boelens, MD1,9, Miguel-Angel Perales, MD6,8, Elena Maryamchik10* and Roni Tamari, MD6,8

1Pediatric Transplantation and Cellular Therapies Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY
2Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
3Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
4Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
5Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
6Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
7Department of Medicine, Weill Cornell Medicine, New York
8Department of Medicine, Weill Cornell Medicine, New York, NY
9Department of Pediatrics, Weill Cornell Medicine, New York, NY
10Transfusion Medicine and Cell Therapy, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Bone marrow (BM) harvested from a related (RD) or unrelated donor (URD) remains a viable graft source for patients (pts) receiving an allogeneic hematopoietic stem cell transplant (allo-HCT). However guidance on minimum TNC/kg & CD34+/kg thresholds to optimize engraftment & a method to best predict graft content are needed.

Methods: All BM products (prdcts) harvested between 1/1/2016 to 6/30/2023 for adult & pediatric (ped) pts were studied (n= 261). Pt, donor, & BM prdct characteristics were collected. For each BM prdct, pre-processing (pre-proc) data was obtained to determine a median pre-proc TNC, TNC/mL, CD34+/mL, and CD34+/TNC % of all BM prdcts & infused TNC & CD34+ content was also recorded. Pt neutrophil (Neutr) & platelet (Plt) engraftment data was collected with Neutr engraftment defined as the first of 3 consecutive days of an absolute neutr count ≥ 500 x 10^3/μl. Plt engraftment was defined as ≥ 20K/μl plts & transfusion independence for ≥ 7 days. Univariable & multivariable analyses (MVAs) using the Fine and Gray model were performed to assess impact of infused TNC/kg (MVA1), CD34+/kg (MVA2), and CD34+/TNC % (MVA3) of conventional BM prdcts on Neutr (n eval pts = 239) & Plt engraftment (n eval pts = 238).

The National Marrow Donor Program’s (NMDP) provided estimate for median TNC/mL of BM (0.183 x 10^8) was used w/ donor weight (wt), the NMDP maximum (max) allowable amount of BM (20mL per donor kg), & a standard max BM volume request (1500mL) to calculate an expected pre-proc TNC for all BM prdcts. The expected TNC for small ped pts was limited to (15 * pt wt) to ensure a TNC/kg cell dose of ≤ 15 x 10^8. An expected pre-proc CD34+ for each BM prdct was then calculated by expected TNC x CD34+/TNC % of all BM prdcts on study. An expectation accuracy (EA) % for both TNC & CD34+ was calculated for each BM prdct (expected / actual pre-proc values observed by our center). TNC & CD34+ EA % of BM prdcts collected by other domestic & international centers were analyzed.

Results: 261 BM prdcts from 259 donors for 258 pts were studied. The BM prdcts had the following pre-proc medians: TNC/mL of 0.136 x 10^8, CD34+/mL of 0.124 x 10^6, & CD34+/TNC % of 0.96. MSKCC harvested 141 (54%) of the BM prdcts and the rest were facilitated by the NMDP: 71 (27%) from 26 domestic centers and 49 (19%) from 28 international centers. The cumulative incidence of Neutr engraftment was 96% (95% CI 92, 98%) by days +30 and +100 after allo-HCT and for Plts it was 48% (95% CI 42,54%) and 91% (95% CI 87,94%) respectively.

Table 1 shows the MVA results testing TNC/kg (MVA1), CD34+/kg (MVA2), CD34+/TNC % (MVA3) & engraftment after allo-HCT w/ conventional BM, indicating Neutr & Plt engraftment is impacted by TNC/kg and CD34+/kg cell dose but not by CD34+/TNC %.

In all 3 MVA models, associations were observed for pt diagnosis [SAA w/ better Plt engraftment vs. ref grp], donor type (≤ 7/8 URD or haploidentical RD w/ worse Neutr & Plt engraftment vs. ref grp), donor ABO incompatibility (Minor w/ better Plt engraftment vs. ref grp), and infusion type [cryopreserved (cryo’ed)/thawed w/ worse Neutr engraftment vs. fresh].

The expectation accuracy (EA) analysis (Wilcoxon rank-sum test) of pre-proc TNC & CD34+ is seen in Table 2. The median expected pre-proc TNC (274) & CD34+ (264) of BM prdcts received from domestic centers & international centers were the same. However BM prdcts from international centers had a lower median actual pre-proc TNC (192) & CD34+ (162), a lower median TNC EA of 74% (vs. 89% for dom centers, p=0.008), & a lower median CD34+ EA of 63% (vs. 93% for dom centers, p<0.001). All BM prdcts combined (n = 120) had a median TNC EA of 83% & a median CD34+ EA of 76%.


This large analysis suggests BM products with a TNC/kg > 2.0 x 10^8 and a CD34+/kg > 2.0 x10^6 were associated with better Neutr & Plt engraftment, as was allo-HCT with an HLA-matched donor. Cryo’ed products were associated with worse Neutr but not Plt engraftment, while SAA & having a BM graft from a donor with a minor ABO incompatibility were associated with better Plt engraftment.

The expectation accuracy analysis suggests BM graft content is often not meeting expectations, highlighting a need for updated guidance on expectations of BM graft content. An update to NMDP’s guidance on estimated TNC/mL of BM or analysis and provision of additional data (e.g., median pre-proc CD34+/mL or CD34+/TNC %) could allow centers to better anticipate TNC & CD34+ BM graft content and help guide donor & graft selection.

Disclosures: Barker: Gamida Cell: Consultancy; New York Blood Center: Consultancy; Merck: Research Funding. Boelens: Bluerock: Consultancy, Honoraria; Omeros: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Immusoft: Consultancy, Honoraria; Advanced Clinical: Honoraria; Bluebird Bio: Honoraria; SmartImmune: Consultancy, Honoraria. Perales: Incyte: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria, Research Funding; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; AbbVie: Consultancy, Honoraria; Allovir: Consultancy; Astellas: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; Exevir: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; VectivBio AG: Consultancy, Honoraria; Vor Biopharma: Consultancy, Honoraria; Adicet: Honoraria; Celgene: Honoraria; Syncopation: Honoraria; Cidara Therapeutics: Consultancy, Other; Medigene: Consultancy, Other; Sellas Life Sciences: Consultancy; NexImmune: Consultancy, Current equity holder in publicly-traded company; Servier: Other; Miltenyi Biotec: Honoraria; DSMB: Other; Allogene: Research Funding.

*signifies non-member of ASH