A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease

TANG Xiang-Feng; LU Wei; JING Yuan-Fang; HUANG You-Zhang; WU Nan-Hai; LUAN Zuo

doi:10.7499/j.issn.1008-8830.2019.06.010

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Chinese Journal of Contemporary Pediatrics ›› 2019, Vol. 21 ›› Issue (6) : 552-557. DOI: 10.7499/j.issn.1008-8830.2019.06.010

CLINICAL RESEARCH

A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease

TANG Xiang-Feng¹, LU Wei¹, JING Yuan-Fang¹, HUANG You-Zhang², WU Nan-Hai¹, LUAN Zuo¹

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Abstract

Objective To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). Methods The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34⁺ cells, and CD3⁺ cells were 14.6×10⁸/kg, 5.86×10⁶/kg, and 2.13×10⁸/kg respectively. Results The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-Ⅱ aGVHD and grade Ⅲ-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. Conclusions Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.

Key words

Chronic granulomatous disease / Haploid hematopoietic stem cell / Cord blood / Transplantation / Child

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TANG Xiang-Feng, LU Wei, JING Yuan-Fang, HUANG You-Zhang, WU Nan-Hai, LUAN Zuo. A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease[J]. Chinese Journal of Contemporary Pediatrics. 2019, 21(6): 552-557 https://doi.org/10.7499/j.issn.1008-8830.2019.06.010

References

[1] Cole T, Pearce MS, Cant AJ, et al. Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation[J]. J Allergy Clin Immunol, 2013, 132(5):1150-1155.
[2] Ahlin A, Fasth A. Chronic granulomatous disease - conventional treatment vs. hematopoietic stem cell transplantation:an update[J]. Curr Opin Hematol, 2015, 22(1):41-45.
[3] Gungor T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease:a prospective multicentre study[J]. Lancet, 2014, 383(9915):436-448.
[4] Wang Y, Chang YJ, Xu LP, et al. Who is the best donor for a related HLA haplotype-mismatched transplant[J]. Blood, 2014, 124(6):843-850.
[5] Marciano BE, Allen ES, Conry-Cantilena C, et al. Granulocyte transfusions in patients with chronic granulomatous disease and refractory infections:the NIH experience[J]. J Allergy Clin Immunol, 2017, 140(2):622-625.
[6] Kang EM, Choi U, Theobald N, et al. Retrovirusgene therapy for X-linked chronic granulomatous disease can achieve stablelong-term correction of oxidase activity in peripheral blood neutrophils[J]. Blood, 2010, 115(4):783-791.
[7] Kang HJ, Bartholomae CC, Paruzynski A, et al. Retroviralgene therapy for X-linked chronic granulomatous disease:results from phaseI/Ⅱ trial[J]. Mol Ther, 2011, 19(1):2092-2101.
[8] Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia[J]. Blood, 2001, 97(10):2962-2971.
[9] 唐湘凤, 卢伟, 井远方, 等. 非血缘脐血干细胞移植治疗X连锁慢性肉芽肿7例[J]. 中国小儿血液与肿瘤杂志, 2016, 21(5):231-236.
[10] Bartelink IH, Belitser SV, Knibbe CA, et al. Immune reconstitution kinetics as an early predictor for mortality using various hematopoietic stem cell sources in children[J]. Biol Blood Marrow Transplant, 2013, 19(2):305-313.
[11] Mattsson J, Ringdén O, Storb R. Graft failure after allogeneic hematopoietic cell transplantation[J]. Biol Blood Marrow Transplant, 2008, 14(1 Suppl 1):165-170.
[12] Ponce DM, Lubin M, Gonzales AM, et al. The use of back-up units to enhance the safety of unrelated donor cord blood transplantation[J]. Biol Blood Marrow Transplant, 2012, 18(4):648-651.
[13] Tsai SB, Liu HT, Shore T, et al. Frequency and risk factors associated with cord graft failure after transplant with single-unit umbilical cord cells supplemented by haploidentical cells with reduced-intensity conditioning[J]. Biol Blood Marrow Transplant, 2016, 22(6):1065-1072.
[14] Kwon M, Martínez-Laperche C, Balsalobre P, et al. Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells[J]. Bone Marrow Transplant, 2014, 49(2):212-218.
[15] Zhou L, Dong LJ, Gao ZY, et al. Haploidentical hematopoietic stem cell transplantation for a case with X-linked chronic granulomatous disease[J]. Pediatr Transplant, 2017, 21(1). doi:10.1111/petr.12861.
[16] Oshrine B, Morsheimer M, Heimall J, et al. Reduced-intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease[J]. Pediatr Blood Cancer, 2015, 62(2):359-361.
[17] Malar R, Sjoo F, Rentsch K, et al. Therapeutic drug monitoring is essential for intravenous busulfan therapy in pediatric hematopoietic stem cell recipients[J]. Pediatr Transplant, 2011, 15(6):580-588.
[18] Raiola AM, Risitano A, Sacchi N, et al. Impact of HLA disparity in haploidentical bone marrow transplantation followed by high-dose cyclophosphamide[J]. Biol Blood Marrow Transplant, 2018, 24(1):119-121.
[19] Hutton JF, Gargett T, Sadlon TJ, et al. Development of CD4⁺CD25⁺FoxP3⁺ regulatory T cells from cord blood hematopoietic progenitor cells[J]. J Leukoc Biol, 2009, 85(3):445-451.
[20] Theil A, Tuve S, Oelschlägel U, et al. Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease[J]. Cytotherapy, 2015, 17(4):473-486.