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01.12.2012 | Letter to the Editor | Ausgabe 1/2012 Open Access

Journal of Hematology & Oncology 1/2012

Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2012
Autoren:
Kyung Taek Hong, Hyoung Jin Kang, Nam Hee Kim, Min Sun Kim, Ji Won Lee, Hyery Kim, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Wichtige Hinweise

Authors' contributions

KTH collected and analyzed the patient data and wrote the manuscript, NHK, MSK collected the patient data, JWL, HK, KDP, HYS, HSA assisted the data interpretation, and HJK designed and coordinated the study. All authors have read and approved the final manuscript.
Abbreviations
SDF1
Stromal cell-derived factor 1
CXCR4
CXC chemokine receptor 4
PBSC
Peripheral blood stem cell
G-CSF
Granulocyte colony stimulating factor.

Letter to the editor

Plerixafor has been introduced for the mobilization of hematopoietic stem cells to peripheral blood, by interfering with the SDF1-CXCR4 interaction. Although it has been FDA-approved in adult patients with non-Hodgkin lymphoma or multiple myeloma [1, 2], the pediatric data usage are scarce, particularly in Asian children [38].
We retrospectively reviewed all 6 patients (3 males, 3 females), who received plerixafor-based mobilization at our center after obtaining the Institutional Review Board approval (H-1108-103-374). They had all previously failed peripheral blood stem cell (PBSC) mobilization by chemotherapy and G-CSF. The patient's characteristics, previous treatments and mobilization chemotherapies are shown. (Table 1) All patients received G-CSF (10 μg/kg) for 4 days, without prior chemotherapy. Then plerixafor (240 μg/kg; Mozobil, Genzyme Inc, Naarden, The Netherlands) and G-CSF (10 μg/kg) were administered subcutaneously, at 10 and 2 hours before each apheresis. CD34+ cells (median, 11.08 × 106/kg; range, 6.34-28.97 × 106/kg) were mobilized successfully in all patients, after 2 to 3 apheresis without immediate complications (for each apheresis: mean, 6.28 × 106/kg: range, 3.17-14.49 × 106/kg). Seven autologous stem cell transplantations were performed, including 1 tandem transplantation, and the results of engraftment were acceptable. (Table 2)
Table 1
Patient Demographics and Prior Treatment Received
Pt #
Dx
Sex
Age
Earlier chemotherapy
Earlier
radiotherapy
1st line mobilization
chemotherapy
1
NBL
M
11
CDDP + VP16 + ADR + CPM, CPM + Topo + VP16
No
CPM + VP16+ GCSF
2
MBL
F
11
CDDP + CPM + VCR, CPM + VCR, Carbo + VP16 + IFM + VCR
IFRT + CSI
Carbo + VP16 + IFM + VCR + GCSF
3
OSA
M
6
CDDP + ADR + MTX, IFM + ADR + MTX
No
CPM + VP16+ GCSF
4
OSA
F
10
CDDP + ADR + MTX, IFM + ADR + MTX, Gemcitabine + Doxetaxel, CPM + Topo + VP16, IFM + Carbo + VP16
No
CPM + VP16+ GCSF
5
MBL
M
10
CDDP + CPM + VCR, CPM + VCR
IFRT + CSI
Carbo + VP16 + IFM + VCR + GCSF
6
ES
F
15
VCR + ADR + CPM, IFM + VP16
No
CPM + VP16+ GCSF
ADR Doxorubicin, Carbo Carboplatin, CDDP Cisplatin, CPM cyclophosphamide, CSI Craniospinal axis irradiation, ES Ewing sarcoma, G-CSF Granulocyte colony stimulating factor, IFM Ifosphamide, IFRT Involved field radiation therapy, LP Leukapheresis, MBL Medulloblastoma, MTX Methotrexate, NBL Neuroblastoma, OSA Osteosarcoma, Pt Patient, Topo Topotecan, VCR Vincristine, VP16 Etoposide
Table 2
PBSC Collection and Engraftment
   
Plerixafor-based PBSC collection
 
Engraftment
Pt #
Prior CD34
yield (106 CD34 + cells/kg)
Days for LP
CD34+ cells(106/kg)
TNC
(108/kg)
Days for LP
TPL #
PBSC infused
(106 CD34+ cells/kg)
ANC > 500/mL (days)
PLT > 20,000/mL
(transfusion-independent)(days)
1
1.24
4
12.64
16.13
3
#1
5.91
10
35
      
#2
3.48
9
197
2
0.18
2
9.52
11.2
2
 
4.8
10
26
3
1.68
2
6.81
10.67
2
 
8.49
10
15
4
0.7
3
6.34
15.1
2
 
7.04
N/A
N/A
5
4
4
28.97
20.25
2
 
17.78
10
N/A
6
0.8
3
15.25
17.83
2
 
3.74
12
18
ANC Absolute Neutrophil Count, LP Leukapheresis, N/A Not Applicable (due to early death), PBSC Peripheral Blood Stem Cell, PLT Platelet, Pt, Patient, TNC Total Nuclear Cells, TPL Transplantation
Patients #1, #3 and #6 were disease-free at the last follow-up (28, 12 and 3 months after transplantation, respectively), however, patient #4 died on day 3, due to sudden cardiac arrest. Interestingly, two medulloblastoma patients (patients #2 and #5) showed serious lung problems, which include spontaneous pneumomediastinum on day 56 and 11, died on day 102 and 89, respectively. The cause of death of both patients showed to be respiratory failure, of which, the pathogen was not revealed by bronchoalveolar lavage or lung biopsy. The pathologic finding was consistent with a diffuse alveolar damage. In our center, 6 other patients who underwent the same radiotherapy and autologous PBSC transplantation, with the same conditioning regimen, but did not receive plerixafor for mobilization, have not shown such fatal pulmonary complication (data not shown). Due to the plerixafor mobilization of the different cell populations, in comparison with G-CSF alone [9, 10], unexpected complications might occur after infusion in susceptible recipients, like the 2 patients that were mentioned above who underwent irradiation around the thoracic area.
In conclusion, we report the first data of Asian pediatric usage of plerixafor for PBSC mobilization, which showed a success rate of 100%, without acute complications. This is a higher success rate than those in the previous pediatric studies [3, 7]. However we experienced two patients with medulloblastoma, who suffered from fatal pulmonary complication. Though the pathogenesis was not understood, further studies are needed to investigate possible complications of plerixafor in pediatric patients.

Conflict of interest

The authors declare that they have no competing interests.

Acknowledgements

We thank the patients, families and clinicians who contributed to this study. This study was supported by grant no 03-2011-0420 from SNUH Research Fund and by grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (A102065)

Authors' contributions

KTH collected and analyzed the patient data and wrote the manuscript, NHK, MSK collected the patient data, JWL, HK, KDP, HYS, HSA assisted the data interpretation, and HJK designed and coordinated the study. All authors have read and approved the final manuscript.

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