Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics
Corresponding Author
Ali Fettah
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Correspondence
Ali Fettah, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey.
Email: [email protected]
Search for more papers by this authorNamık Özbek
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorMeltem Özgüner
Stem Cell Research Laboratory, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorFatih Azık
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorPamir Işık
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorZekai Avcı
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorNeşe Yaralı
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorDuygu Uçkan
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Stem Cell Research Laboratory, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorBahattin Tunç
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorCorresponding Author
Ali Fettah
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Correspondence
Ali Fettah, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey.
Email: [email protected]
Search for more papers by this authorNamık Özbek
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorMeltem Özgüner
Stem Cell Research Laboratory, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorFatih Azık
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorPamir Işık
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorZekai Avcı
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorNeşe Yaralı
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorDuygu Uçkan
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Stem Cell Research Laboratory, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorBahattin Tunç
Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Ankara Children Hematology Oncology Research Hospital, Ankara, Turkey
Search for more papers by this authorAbstract
The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G-CSF for stem cell mobilization (G-CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106/L (0.02-0.21) in SS-BM donors and 0.18×106/L (0.09-0.67) in GP-BM donors (P=.03). Median of CD34+ cell count given to recipients was 2.6×106/recipient body weight (1.3-19.3) in SS-BM yields and 3.8×106/recipient body weight (1.1-10.2) in GP-BM yields, respectively. Multiple regression analysis showed that donor height and pre-G-CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors.
References
- 1Kim H, Kang HJ, Lee JW, Park KD, Shin HY, Ahn HS. Early engraftment of G-CSF-primed allogeneic bone marrow transplantation in pediatric patients regardless of donor-recipient weight differences. Ann Hematol. 2012; 91: 751–758.
- 2Cutler C, Giri S, Jeyapalan S, Paniagua D, Viswanathan A, Antin JH. Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol. 2001; 19: 3685–3691.
- 3Storek J, Gooley T, Siadak M, et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease. Blood. 1997; 90: 4705–4709.
- 4Ince EU, Ileri T, Dogu F, et al. The impact of donor age and sex on the nucleated cell count and CD34 count in healthy bone marrow donors. Pediatr Transplant. 2015; 19: 385–390.
- 5Suzuya H, Watanabe T, Nakagawa R, et al. Factors associated with granulocyte colony-stimulating factor-induced peripheral blood stem cell yield in healthydonors. Vox Sang. 2005; 89: 229–235.
- 6Pastore D, Specchia G, Mestice A, et al. Good and poor CD34 + cells mobilization in acute leukemia: analysis of factors affecting the yield of progenitor cells. Bone Marrow Transplant. 2004; 33: 1083–1087.
- 7Carral A, De La Rubia J, Martín G, et al. Factors influencing the collection of peripheral blood stem cells in patients with acute myeloblastic leukemia and non-myeloid malignancies. Leuk Res. 2003; 27: 5–12.
- 8Nowrousian MR, Waschke S, Bojko P, et al. Impact of chemotherapy regimen and hematopoietic growth factor on mobilization and collection of peripheral blood stem cells in cancer patients. Ann Oncol. 2003; 14: i29–i36.
- 9Delgado J, Fernandez-Jimenez MC, Martinez A, et al. Analysis of factors affecting PBPC collection in low-weight children with malignant disorders. Cytotherapy. 2004; 6: 43–49.
- 10Brown RA, Adkins D, Goodnough LT, et al. Factors that influence the collection and engraftment of allogeneic peripheral-blood stem cells in patients with hematologic malignancies. J Clin Oncol. 1997; 15: 3067–3074.
- 11Shimizu N, Asai T, Hashimoto S, et al. Mobilization factors of peripheral blood stem cells in healthy donors. Ther Apher. 2002; 6: 413–418.
- 12Vasu S, Leitman SF, Tisdale JF, et al. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in anethnically diverse population. Blood. 2008; 112: 2092–2100.
- 13Anderlini P, Przepiorka D, Seong C, et al. Factors affecting mobilization of CD34+ cells in normal donors treated with filgrastim. Transfusion. 1997; 37: 507–512.
- 14Miflin G, Charley C, Stainer C, Anderson S, Hunter A, Russell N. Stem cell mobilization in normal donors for allogeneic transplantation: analysis of safety and factors affecting efficacy. Br J Haematol. 1996; 95: 345–348.
- 15Grigg AP, Roberts AW, Raunow H, et al. Optimizing dose and scheduling of filgrastim (granulocyte colony-stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers. Blood. 1995; 86: 4437–4445.
- 16Frangoul H, Nemecek ER, Billheimer D, et al. A prospective study of G-CSF primed bone marrow as a stem-cell source for allogeneic bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium (PBMTC) study. Blood. 2007; 110: 4584–4587.
- 17Morton J, Hutchins C, Durrant S. Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells. Blood. 2001; 98: 3186–3191.
- 18Grupp SA, Frangoul H, Wall D, Pulsipher MA, Levine JE, Schultz KR. Use of G-CSF in matched sibling donor pediatric allogeneic transplantation: a consensus statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee. Pediatr Blood Cancer. 2006; 46: 414–421.
- 19Pulsipher MA, Nagler A, Iannone R, Nelson RM. Weighing the risks of G-CSF administration, leukopheresis, and standard marrow harvest: ethical and safety considerations for normal pediatric hematopoietic cell donors. Pediatr Blood Cancer. 2006; 46: 422–433.
- 20Ji SQ, Chen HR, Xun CQ, Wang HX, Pan SP, Xiao MH. The effect of G-CSF-stimulated donor marrow on engraftment and incidence of graft-versus-host disease in allogeneic bone marrow transplantation. Clin Transplant. 2001; 15: 317–323.
- 21Takeyama K, Ohto H. PBSC mobilization. Transfus Apher Sci. 2004; 31: 233–243.
- 22Singhal S, Powles R, Treleaven J, et al. A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2x10(6) CD34 + cells/kg be considered the minimum threshold? Bone Marrow Transplant. 2000; 26: 489–496.
- 23Lysák D, Koza V, Jindra P. Factors affecting PBSC mobilization and collection in healthy donors. Transfus Apher Sci. 2005; 33: 275–283.
- 24Zhang C, Chen XH, Zhang X, et al. Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings. Transfus Med. 2010; 20: 169–177.
- 25De La Rubia J, Arbona C, De Arriba F, et al. Analysis of factors associated with low peripheral blood progenitor cell collection in normal donors. Transfusion. 2002; 42: 4–9.
- 26Ings SJ, Balsa C, Leverett D, Mackinnon S, Linch DC, Watts MJ. Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony-stimulating factor (G-CSF): Impact of age, sex, donor weight and type of G-CSF used. Br J Haematol. 2006; 134: 517–525.
- 27Díaz MA, Sevilla J, De La Rubia J, et al. Factors predicting peripheral blood progenitor cell collection from pediatric donors for allogeneic transplantation. Haematologica. 2003; 88: 919–922.
- 28Li Y, Chang Y, Xu L, Zhang X, Huang X. Negative association of donor age with CD34+cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests. Chin Med J (Engl). 2014; 127: 3597–3601.
- 29Papayannopoulou T. Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization. Blood. 2004; 103: 1580–1585.
- 30Fukuda S, Broxmeyer HE, Pelus LM. Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1alpha(CXCL12)/CXCR4 axis. Blood. 2005; 105: 3117–3126.
- 31Pelus LM, Bian H, Fukuda S, Wong D, Merzouk A, Salari H. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp Hematol. 2005; 33: 295–307.
- 32Perez LE, Alpdogan O, Shieh JH, et al. Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice. Exp Hematol. 2004; 32: 300–307.
- 33Avecilla ST, Hattori K, Heissig B, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004; 10: 64–71.
- 34Nomura S, Inami N, Kanazawa S, Iwasaka T, Fukuhara S. Elevation of platelet activation markers and chemokines during peripheral blood stem cell harvest with G-CSF. Stem Cells. 2004; 22: 696–703.
- 35Wang TF, Wen SH, Chen RL, et al. Factors associated with peripheral blood stem cell yield in volunteer donors mobilized with granulocyte colony-stimulating factors: the impact of donor characteristics and procedural settings. Biol Blood Marrow Transplant. 2008; 14: 1305–1311.
Citing Literature
