Hematopoietic Stem Cell Transplantation in Pediatric Acute Myelogenous Leukemia: Relevance of the Stem Cell Source to the Transplant Outcome

Hye Ryoung Yi; Dong Kyun Han; Hee Jo Baek; Young Ok Kim; Seok Joo Kim; Eun Song Song; Hoon Kook; Tai Ju Hwang

doi:10.5045/kjh.2005.40.4.242

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Yi, Han, Baek, Kim, Kim, Song, Kook, and Hwang: Hematopoietic Stem Cell Transplantation in Pediatric Acute Myelogenous Leukemia: Relevance of the Stem Cell Source to the Transplant Outcome

Original Article

Korean J Hematol 2005;40(4):242-253.

Published online: 21 December 2005

DOI: https://doi.org/10.5045/kjh.2005.40.4.242

Hematopoietic Stem Cell Transplantation in Pediatric Acute Myelogenous Leukemia: Relevance of the Stem Cell Source to the Transplant Outcome

Hye Ryoung Yi, M.D., Dong Kyun Han, M.D., Hee Jo Baek, M.D., Young Ok Kim, M.D., Seok Joo Kim, M.D., Eun Song Song, M.D., Hoon Kook, M.D., Tai Ju Hwang, M.D.

Department of Pediatrics, Chonnam National University Medical School, Blood & Marrow Transplantation Center, Chonnam National University Hwasun Hospital, Gwangju, Korea

Correspondence to: Hoon Kook, M.D. Department of Pediatrics, Chonnam National University Medical School 160, Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeonnam 519-809, Korea Tel: +82-61-379-7693, Fax: +82-61-379-7697 E-mail: hoonkook@chonnam.ac.kr

Received 3 November 2005 Revised 5 December 2005 Accepted 10 December 2005

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Postremission therapy is critical for achieving longterm survival in the patients with acute myelogenous leukemia (AML). Allogeneic bone marrow transplantation during the first complete remission (CR) with using a HLA-identical sibling donor may offer the best chance for longterm leukemia-free survival. The patients without matched siblings have several treatment options. The aim of this study was to compare the clinical outcomes after matched sibling transplantation (MST), unrelated stem cell transplantation (non-MST), or autologous peripheral blood stem cell transplantation (APBSCT) as a postremission therapy for children with AML.

Methods

Thirty four hematopoietic stem cell transplantations (SCT) in 32 children with AML were performed between June, 1996 and December, 2004. Two patients who failed at prior APBSCT underwent a 2nd unrelated transplantations. The disease status at the time of transplantation, the conditioning regimen, prophylaxis for graft-versus-host disease (GVHD), the incidence of GVHD, complications, the cause of death, the overall survival and the event-free survival were retrospectively compared in relation to the stem cell sources.

Results

There were 19 males and 13 females with a median age of 8 yr 10 mo. The median follow-up was 17 mo. Twenty-eight cases were transplanted during CR1. Most (5/6) of patients other than the patients who were in CR1 were allocated in the non-MST group. APBSCT was done in 17 cases, and allo-transplants were done in 17 cases, which included MSTs in 10, matched-unrelated BM transplants in 5, haploidentical CD34+selected peripheral blood transplant in 1, and 1-antigen mismatch unrelated cord blood transplantation in 1. Acute GvHD ≥ than Grade 2 was found in 20% of the MST cases vs. 85.7% in the non-MST cases (P＜.01). The two-year cumulative relapse risks were 46.4% in the APBSCT cases, 20% in the MST cases and 31.5% in the non-MST cases. The Kaplan-Meier 2-year EFS in all cases was 55.7%: 46.3% in the APBMT cases, 80.0% in the MST cases and 68.6% in the non-MST cases, despite the higher proportion of high risk patients in the non-MST group.

Conclusion

This study indicated that MST was the best option for pediatric AML. For patients without matched siblings, the patients with unrelated transplants fared better, had better survival and a lower relapse rate than the APBSCT patients. However, a further prospective, randomized study that incorporates a larger number of patients and a cord blood transplant arm is necessary to definitely determine the best option for pediatric

Keywords: Acute myelogenous leukemia, Stem cell transplantation, Stem cell source

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Fig. 1.

Kaplan-Meier analysis of (A) Overall survival and (B) Event free survival by stem cell source.

Fig. 2.

Cumulative incidence of relapse by stem cell source.

Table 1.

Summary of patient's characteristics and stem cell transplantation

No. of patients
Male: Female	20: 14
Age in years at diagnosis, median (range)	8.8 (1.3～16.9)
Age in years at transplantation (range)	9.3 (1.5～14.5)
Autologous SCT (PB/BM)	16/1
Allogeneic SCT
MST	10
Non-MST	7
Umbilical cord blood (5/6 match)	1
HLA-matched unrelated BM	5
Haploidentical CD34+selected PB	1
Cytogenetics	APBSCT (n=17)	Allo-SCT (n=17)
Normal karyotype	0	2
t(8: 21)	3	0
t(15: 17)	2	1
t(11: 17)	1	0
t(3: 3)	1	0
Trisomy 8	0	1
Trisomy 22	0	1
+8del (12) p (13)	0	1
Inv (16)	0	1
MLL gene rearrangement	0	1
CBF/MYH1	0	1
Add (9)	1	0
No growth	9	8
Conditioning regimen
Autologous stem cell transplantation
BCNU, Cytoxan, VP-16, Ara-C	13
Busulfan, VP-16, Ara-C	3
Cytoxan, VP-16, Ara-C	1
Allogeneic stem cell transplantation
Busulfan, Cytoxan	10
TBI, Cytoxan, Ara-C	3
Fludarabine, Busulfan, ATG	3
TBI, Cytoxan, VP-16, Ara-C	1

Abbreviations: MST, matched sibling transplantation; VP-16, etoposide; Ara-C, cytosine arabinoside; TBI, total body irradiation; Cytoxan, cyclophosphamide; SCT, stem cell transplantation; BM, bone marrow; PB, peripheral blood.

Table 2.

FAB classification

	APBSCT	Allo-SCT	Total	%
M0		1	1	2.9
M1		0	0	0.0
M2	12	3	15	44.0
M3	2	1	3	9.1
M4	1	8	9	26.4
M5		2	2	5.6
M6		1	1	2.9
M7	2	1	3	9.1
Total	17	17	34	100.0

Abbreviations: APBSCT, autologous peripheral blood stem cell transplantation; Allo-SCT, allogeneic stem cell transplantation.

Table 3.

Disease status at transplant by stem cell source

	APBSCT	MST	Non-MST	Total
CR1	16	10	2	28
CR2	1	0	2	3
CR3	0	0	1	1
Partial remission	0	0	2	2
% of high risk^∗	5.8	0	71.4	17.5

^∗ Disease status other than CR1. Abbreviations: CR1, 1st complete remission; CR2, 2nd complete remission; CR3, 3rd complete remission; APB-SCT, autologous peripheral blood stem cell transplantation; MST, matched sibling transplantation.

Table 4.

Patient characteristics by stem cell sources

	Total	APBSCT	Total	Allo-SCT MST	non-MST	P value
M:F ratio	20: 14	12: 5	8: 9	2: 8	6: 1
Age in years at diagnosis	8.8	9.9	8	8.1	9	.81
Age in years at transplantation	9.3	10.7	8.2	8.2	10.1	.75
Follow-up months median (range)	17	17	17	13.5	20
	(2～107)	(2～93)	(3～107)	(5～107)	(3～34)
Days of admission median (range)	44	44	46	42	50	.51
	(32～107)	(32～167)	(36～80)	(36～60)	(36～80)
Initial WBC (×10³) median (range)	11.9	11.9	12.0	9.8	30.0	.75
	(1.32～172.5)	(2.29～172.9) (	(1.52～172.9)	(15～104)	(4.6～62.8)
Transplantation, median
Total cell count (×10⁸/kg)	6.6	5.6	6.8	7.2	3.2	.03
Mononuclear cell (×10⁸/kg)	5.2	6.7	4.5	4.6	2.7	.006
CD34+cell (×10⁶/kg)	5.1	4.8	6.0	6.8	5.0	.174
CFU-GM (×10⁵/kg)	3.0	2.4	5.8	6.4	4.3	.006
Days of engraftment, median
ANC≥500/μL	16	15.0	17.5	16.5	17.5	.613
ANC≥1,000/μL	19	17.5	20.0	20.0	19.5	.407
PLT≥20,000/μL	29	29	28.0	28.0	28.5	.426
PLT≥50,000/μL	35	35	31.0	32.5	31.0	.505

Abbreviations: ANC, absolute neutrophil count; PLT, platelets; APBSCT, autologous peripheral blood stem cell transplantation; Allo-SCT, allogeneic stem cell transplantation; MST, matched sibling transplantation; WBC, white blood cell counts.

Table 5.

Complication after stem cell transplantation by stem cell source

	Auto (n=17)	MST (n=10)	Non-MST (n=7)	P value
CMV				.10
CMV culture	1	0	2
CMV antigenemia	0	0	2
CMV disease	1	0	2
Bacterial infection	0	0	3	.40
Fungal infection	6	0	0	.11
Interstitial pneumonitis	0	1	1	.48
VOD	0	0	0
Hemorrhagic cystitis (No)	2	2	1	.90
GI toxicity (stomatitis, N & V, diarrhea)	4	1	2	.57
Life threatening bleeding	0	0	1^∗	.60
Acute GVHD (%)		2 (20)	7 (100)	＜.01
Onset days (median/range)		16 (2～30)	16 (1～27)	.29
≥Grade II		2 (20.0)	6 (85.7)^∗
Chronic GVHD		1 (10%)	3 (42%)	＜.01
Onset days (median/range)		NK	197.7 (132～277)
Limited/Extensive		1/0	1/2

^∗ 1 patient, Grade IV involving skin, gut. Abbreviations: Auto, autologous peripheral blood stem cell transplantation; MST, matched sibling transplantation; CMV, cytomegalovirus; VOD, venoocclusive disease; N & V, nausea and vomiting; GVHD, graft versus host disease; NK, not known.

Table 6.

Comparison of cause of death by stem cell source

	APBSCT (n=17)	MST (n=10)	Non-MST (n=7)	P-value
Number of Patients died	10	2	2	.79
Cause of death
Recurrence/persistence of primary disease	9 (90%)	2 (100%)	2 (100%)
ARF, CMV disease	1	0	0

Abbreviations: APBSCT, autologous peripheral blood stem cell transplantation; MST, matched sibling transplantation; ARF, acute renal failure; CMV, cytomegalovirus.

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