Periferal kan kök hücre transplantasyonu uygulanan hastalarda destek tedavisinde transplant sonrası +5. günde G-CSF uygulamak avantajlıdır

Makalenin İngilizce İsmi: 
Applying G-CSF on post-transplant +5th day is advantageous on supportive treatment in patients undergoing peripheral blood stem cell transplantation
Makale İçerik Bilgileri
Makale Dili: 
İngilizce
Anahtar Kelimeler: 
Otolog periferik kök hücre nakli
engraftman
G-CSF
büyüme faktörü
destek tedavi
Türkçe Özet: 

Periferik kök hücre naklinden sonra +5. günde granülosit koloni stimüle edici faktör (G-CSF) uygulanmasının hematolojik engraftman ve destek tedavi gereksinimleri açılarından rolü araştırıldı. Solid ve hematolojik maligniteli 42 ardışık hasta G-CSF uygulanmasına göre iki kohort gruba ayrıldı. Yirmi yedi hastaya G-CSF (5 μg/kg/day) nakilden sonraki +5. günden nötrofil engraftmanına kadar verildi. On beş hastadan oluşan kontrol grubuna ise nakil sonrasında GCSF verilmedi. Hastaların hepsine sitaferezle toplanan en az 2X106/kg sayıda CD34+ hücre verildi. Her iki grup arasında, G-CSF alan grup lehine olmak üzere nötrofil engraftman zamanı (10.55±1.21 karşın 11.93±2.89 gün; p=0.04), ateşli gün sayısı (3.33±2.66 karşın 5±2.95 gün; p=0.03) ve antibiyotik tedavisi gerektiren gün sayısı (7.07±3.46 karşın 11.87±3.74 gün; p<0.001) açılarından istatistiksel anlamlı farklılık saptandı; ancak hospitalizasyon süresi (13.30±4.79 ve 13.53±2.56 gün; p=0.26), trombosit engraftman zamanı (12.22±2.79 ve 13.40±3.89 gün; p=0.26) ve eritrosit transfüzyon ihtiyacı bakımından anlamlı farklılık saptanmadı. Trombosit transfüzyon ihtiyacı ise G-CSF desteği yapılan ve yapılmayan gruplar arasında istatistiksel açıdan anlamlı farklı bulundu (1.27±0.96 vs 0.56±0.75, p=0.01). Bu çalışma nakilden sonra +5. günde G-CSF başlanmasının nötrofil engraftmanını hızlandırdığını, ateşli gün sayısını ve antibiyotik ihtiyacını azalttığını göstermektedir.

Key Words: 
Autologous peripheral stem cell transplantation
engraftment
G-CSF
growth factor
supportive treatment
İngilizce Özet: 

The role of granulocyte-colony stimulating factor (G-CSF)
administration on day +5 after peripheral blood stem cell
transplantation in terms of hematologic engraftment and
supportive treatment need has been evaluated. Forty two
consecutive patients with solid and hematological malignancies were enrolled in two groups depending on G-CSF administration. Twenty seven patients were given G-CSF (5
µg/kg/day) from day +5 after the transplantation until the
achievement of neutrophil engraftment. Post-transplant GCSF was not given to the control arm of 15 patients. A number of at least 2X10
6
CD34
+
cells per kilogram collected by
cytapheresis were given to all patients. A significant difference was found between the two groups in favor of G-CSF
receiving group, in terms of neutrophil engraftment time
(10.55±1.21 vs 11.93±2.89 days; p=0.04), number of days
with fever (3.33±2.66 vs 5±2.95 days; p=0.03) and number of
days requiring antibiotic therapy (7.07±3.46 vs 11.87±3.74
days; p<0.001), whereas no statistically significant differences were noted in terms of hospitalization period
(13.30±4.79 and 13.53±2.56 days; p=0.26), platelet engraftment time (12.22±2.79 and 13.40±3.89 days; p=0.26) and
erythrocyte transfusion need; however, platelet transfusion
need was statistically significant between the groups with
and without G-CSF support (1.27±0.96 vs 0.56±0.75, p=0.01).
This study revealed that starting G-CSF on day +5 may fasten the neutrophil engraftment, decrease the number of
days with fever and decrease the need for antibiotic therapy in post-transplant period.

Yazar Bilgileri
2. Yazar
Yazar Adı: 
Kamil Başköy
3. Yazar
Yazar Adı: 
Selmin Ataergin
4. Yazar
Yazar Adı: 
Ahmet Özet
5. Yazar
Yazar Adı: 
Mustafa Öztürk
6. Yazar
Yazar Adı: 
Okan Kuzhan
7. Yazar
Yazar Adı: 
Şeref Kömürcü
8. Yazar
Yazar Adı: 
Bekir Öztürk
Makale Künye Bilgisi
Makalenin Yayımlandığı Dergi: 
Gülhane Tıp Dergisi
Makale Yayın Yılı: 
2007
Cilt/Sayı: 
49
Sayı: 
3
Sayfa Aralığı: 
157-162
Referanslar: 

1. Beaujean F, Bourhis JH, Bayle C, et al. Successful cryopreservation of purified autologous CD34+ cells: influence of freezing parameters on cell recovery and engraftment. Bone Marrow Transplant 1998; 22: 1091-1096.
2. Colombat P, Delain M, Desbois I, et al. Granulocytemacrophage colony-stimulating factor accelerates hematopoietic recovery after autologous bone marrow or
peripheral blood progenitor cell transplantation and highdose chemotherapy for lymphoma. Bone Marrow Transplant 1996; 18: 293-299.
3. Gorin NC, Lopez M, Laporte JP, et al. Preparation and
successful engraftment of purified CD34+ bone marrow
progenitor cells in patients with non-Hodgkin's lymphoma. Blood 1995; 85: 1647-1654.
4. Jansen J, Thompson EM, Hanks S, et al. Hematopoietic
growth factor after autologous peripheral blood transplantation: comparison of G-CSF and GM-CSF. Bone
Marrow Transplant 1999; 23: 1251-1256.
5. McQuaker IG, Hunter AE, Pacey S, Haynes AP, Iqbal A,
Russell NH. Low-dose filgrastim significantly enhances
neutrophil recovery following autologous peripheralblood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit. J Clin Oncol 1997; 15: 451-457.
6. Spitzer G, Adkins DR, Spencer V, et al. Randomized
study of growth factors post-peripheral-blood stem-cell
transplant: neutrophil recovery is improved with modest
clinical benefit. J Clin Oncol 1994; 12: 661-670.
7. Tricot G, Jagannath S, Vesole D, et al. Peripheral blood
stem cell transplants for multiple myeloma: identification
of favorable variables for rapid engraftment in 225
patients. Blood 1995; 85: 588-596.
8. Bence-Bruckler I, Bredeson C, Atkins H, et al. A randomized trial of granulocyte colony-stimulating factor
(Neupogen) starting day 1 vs day 7 post-autologous stem
cell transplantation. Bone Marrow Transplant 1998; 22:
965-969.
9. Bolwell BJ, Pohlman B, Andresen S, et al. Delayed GCSF after autologous progenitor cell transplantation: a
prospective randomized trial. Bone Marrow Transplant
1998; 21: 369-373.
10. Faucher C, Le Corroller AG, Chabannon C, et al.
Administration of G-CSF can be delayed after transplantation of autologous G-CSF-primed blood stem cells: a
randomized study. Bone Marrow Transplant 1996; 17:
533-536.
11. Piccirillo N, Sica S, Laurenti L, et al. Optimal timing of
G-CSF administration after CD34+ immunoselected
peripheral blood progenitor cell transplantation. Bone
Marrow Transplant 1999; 23: 1245-1250.
12. Peters W. Bone marrow transplantation. In: Holland TF,
Bast RC, Morten DL, Frei E, Küfe DW, Weichselbaum
RR (eds). Cancer Medicine. 4th ed. Baltimore: Williams
& Wilkins, 1997: 1279-1295.
13. Ojeda E, Garcia-Bustos J, Aguado MJ, et al. A prospective
randomized trial of granulocyte colony-stimulating factor
therapy after autologous blood stem cell transplantation in
adults. Bone Marrow Transplant 1999; 24: 601-607.
14. de Azevedo AM, Nucci M, Maiolino A, et al. A randomized multicenter study of G-CSF starting on day +1 vs
day +5 after autologous peripheral blood progenitor cell
transplantation. Bone Marrow Transplant 2002; 29: 745-
751.
15. Hornedo J, Sola C, Solano C, et al. (SOLTI Group) The
role of granulocyte colony-stimulating factor (G-CSF) in
the post-transplant period. Bone Marrow Transplant
2002; 29: 737-743.

Introduction
Early hematopoietic recovery is crucial in reducing
mortality and morbidity rates in patients undergoing
peripheral blood stem cell transplantation (PBSCT)
and defining the success of the transplantation. Many
hematopoietic growth factors affect hematopoietic
recovery and different administration protocols are still
* Department of Oncology, Gülhane Military Medical Academy
**Department of Internal Medicine, Gülhane Military Medical Academy
Reprint request: Dr. Fikret Arpacý, Department of Oncology, Gülhane
Military Medical Academy, Etlik-06018, Ankara, Turkey
E-mail: farpaci@gata.edu.tr
Date submitted: April 24, 2007
Accepted: July 05, 2007
ARAÞTIRMA/ORIGINAL ARTICLE Gülhane Týp Dergisi 2007; 49: 157-162
© Gülhane Askeri Týp Akademisi 2007
Summary
The role of granulocyte-colony stimulating factor (G-CSF)
administration on day +5 after peripheral blood stem cell
transplantation in terms of hematologic engraftment and
supportive treatment need has been evaluated. Forty two
consecutive patients with solid and hematological malignancies were enrolled in two groups depending on G-CSF administration. Twenty seven patients were given G-CSF (5
µg/kg/day) from day +5 after the transplantation until the
achievement of neutrophil engraftment. Post-transplant GCSF was not given to the control arm of 15 patients. A number of at least 2X10
6
CD34
+
cells per kilogram collected by
cytapheresis were given to all patients. A significant difference was found between the two groups in favor of G-CSF
receiving group, in terms of neutrophil engraftment time
(10.55±1.21 vs 11.93±2.89 days; p=0.04), number of days
with fever (3.33±2.66 vs 5±2.95 days; p=0.03) and number of
days requiring antibiotic therapy (7.07±3.46 vs 11.87±3.74
days; p<0.001), whereas no statistically significant differences were noted in terms of hospitalization period
(13.30±4.79 and 13.53±2.56 days; p=0.26), platelet engraftment time (12.22±2.79 and 13.40±3.89 days; p=0.26) and
erythrocyte transfusion need; however, platelet transfusion
need was statistically significant between the groups with
and without G-CSF support (1.27±0.96 vs 0.56±0.75, p=0.01).
This study revealed that starting G-CSF on day +5 may fasten the neutrophil engraftment, decrease the number of
days with fever and decrease the need for antibiotic therapy in post-transplant period.
Key words: Autologous peripheral stem cell transplantation,
engraftment, G-CSF, growth factor, supportive treatment
Özet
Periferal kan kök hücre transplantasyonu uygulanan
hastalarda destek tedavisinde transplant sonrasý +5.
günde G-CSF uygulamak avantajlýdýr
Periferik kök hücre naklinden sonra +5. günde granülosit
koloni stimüle edici faktör (G-CSF) uygulanmasýnýn hematolojik engraftman ve destek tedavi gereksinimleri açýlarýndan rolü araþtýrýldý. Solid ve hematolojik maligniteli 42
ardýþýk hasta G-CSF uygulanmasýna göre iki kohort gruba
ayrýldý. Yirmi yedi hastaya G-CSF (5 µg/kg/day) nakilden
sonraki +5. günden nötrofil engraftmanýna kadar verildi. On
beþ hastadan oluþan kontrol grubuna ise nakil sonrasýnda GCSF verilmedi. Hastalarýn hepsine sitaferezle toplanan en az
2X10
6
/kg sayýda CD34
+
hücre verildi. Her iki grup arasýnda,
G-CSF alan grup lehine olmak üzere nötrofil engraftman
zamaný (10.55±1.21 karþýn 11.93±2.89 gün; p=0.04), ateþli
gün sayýsý (3.33±2.66 karþýn 5±2.95 gün; p=0.03) ve antibiyotik tedavisi gerektiren gün sayýsý (7.07±3.46 karþýn
11.87±3.74 gün; p<0.001) açýlarýndan istatistiksel anlamlý
farklýlýk saptandý; ancak hospitalizasyon süresi (13.30±4.79
ve 13.53±2.56 gün; p=0.26), trombosit engraftman zamaný
(12.22±2.79 ve 13.40±3.89 gün; p=0.26) ve eritrosit transfüzyon ihtiyacý bakýmýndan anlamlý farklýlýk saptanmadý.
Trombosit transfüzyon ihtiyacý ise G-CSF desteði yapýlan ve
yapýlmayan gruplar arasýnda istatistiksel açýdan anlamlý farklý bulundu (1.27±0.96 vs 0.56±0.75, p=0.01). Bu çalýþma
nakilden sonra +5. günde G-CSF baþlanmasýnýn nötrofil
engraftmanýný hýzlandýrdýðýný, ateþli gün sayýsýný ve antibiyotik ihtiyacýný azalttýðýný göstermektedir.
Anahtar kelimeler: Otolog periferik kök hücre nakli,
engraftman, G-CSF, büyüme faktörü, destek tedavi158 · Eylül 2007 · Gülhane TD Arpacý et al.
under investigation in terms of the utility of growth factors to accelerate engraftment process; however the
standard day on which growth factor administration
should be started is not yet well defined (1-7).
Recent studies comparing early and late granulocytecolony stimulating factor (G-CSF) administration on
day +1 and +7 post-transplant revealed that early
hematological engraftment achievement was not established as expected in cases with early growth factor
administration (8-11).
G-CSF administration during PBSCT was shown to
achieve neutrophil engraftment one week earlier
approximately, but no effect on platelet engraftment and
on mortality caused by infectious diseases was noted
(12).
In this prospective study, we compared the two treatment groups with one receiving G-CSF on day +5 after
the autologous transplantation and the other without
any growth factor support. We investigated the results
of the groups in terms of hematopoietic recovery and
post-transplant supportive care requirements.
Material and Methods
Patients: Forty two consecutive patients were included in this interference investigation. All patients were
given written informed consent form. The first group
(from January 1999 to December 1999) (fifteen
patients) were not given G-CSF in post-transplant period; while in the second group (from January 2000 to
December 2000) twenty seven patients received G-CSF
on a dose of 5 µg/kg per day, intravenously or subcutaneously from the day +5 after the infusion of stem cells
until the achievement of neutrophil engraftment. All
patients were informed about the study and written
consent was taken from each. Patients' diagnoses were
breast cancer (12 patients), osteosarcoma (4 patients),
testicular cancer (6 patients), Ewing's sarcoma (2
patients), primitive neuroectodermal tumor (PNET) (1
patient), extragonadal germ cell tumor (1 patient),
Hodgkin's disease (8 patients), non-Hodgkin's lymphoma (6 patients) and multiple myeloma (2 patients).
(Tables I,II,III).
Cytapheresis of stem cells and cryopreservation: Stem cells
were mobilized by G-CSF on a dose of 10-15 µg/kg per
day subcutanously or intravenously (Filgrastim,
Neupogen®, Roche, Basel, Switzerland) fourteen days
after the completion of the chemotherapy. Then,
apheresis was done using Cobe Spectra cell seperator
(COBE Lakewood, Co, USA) after the administration
of G-CSF on days 4 to 6. Apheresis was done after six
to eight hours after the last dose of G-CSF.
Mononuclear cells obtained by cytapheresis were then
cryopreserved in liquid nitrogen at -197 °C with final
concentration of 10% dimethylsulfoxide (DMSO).
Flow-cytometry: Apheresis product containing 1X106
mononuclear cells per kilogram were incubated within
10 cc fluorescein isothyocyanate-conjugated anti-CD34
antibody (Becton Dickinson, Heidelberg, Germany).
Isotope-identic antibodies were used as controls. A
minimum of 50X109
/L cells were counted via flowcytometry (FACScan, Becton Dickinson, Heidelberg,
Germany) and CD34+ cell number was detected thereafter.
Conditioning regimens: In patients receiving G-CSF on
day +5, the conditioning regimens consisted of ICE
(ifosfamide, carboplatin and etoposide) in ten patients,
BEAM (BCNU, etoposide, cytarabine and melphalan)
in five patients, TCM (thiotepa, carboplatin and melphalan) in one patient, CNV (cyclophosphamide,
mitoxantrone and etoposide) in seven patients, melphalan in one patient, CyEAM (cyclophosphamide, etoposide, cytosine arabinoside and melphalan) in one
patient, total body irradiation (TBI-12Gy/6 fr/3 daysCo60 theratron machine) with cyclophosphamide in
two patients.
In the other group without G-CSF support, the regimens included ICE (4 patients), BEAM (6 patients),
CNV (4 patients) and L-PAM (1 patient).
Stem cell reinfusion: The day after the completion of
the conditioning regimen, the apheresis product was
heated in bain-marie until 37 °C and reinfused via the
central venous catheter into the patient.
Diphenhydramine 50 mg and methylprednisolone 1
mg/kg were applied intravenously 30 minutes before
the infusion.
Growth factor administration: In the second group who
were given growth factor, G-CSF was used until the
neutrophil count was over or equal 1X109
/L for three
consecutive days.
Supportive treatment after the transplantation: Patients
were stayed in isolated rooms sterilized via ultraviolet
light after the stem cell infusion. Patients received
ciprofloxacin per oral route for enteric decontamination
prophylaxis during the neutropenic period. All patients
were given the same febrile neutropenia protocol. Wide
spectrum parenteral antibiotics were initiated in case of
continuous fever over 38.1 °C for two hours or clinically suspected infections, after confirmation with all necessary cultures (blood cultures from both arms, and
urine, stool and sputum cultures, if needed). The
antibiotic treatment was changed if any pathogen was
isolated microbiologically according to the antibiogramCilt 49 · Sayý 3 · Gülhane TD G-CSF on post-transplant +5th day · 159
result. If no pathogen was isolated, the initial empirical
antibiotic treatment was continued until neutrophil
recovery. No patient was given granulocyte infusion.
Thrombopheresis was performed according to the
groups. In G-CSF receiving group, platelet transfusion
was given, if platelet count was under or equal to
10X109
/L, while in the other group not receiving GCSF, trombopheresis was done if platelet count was
under or equal to 20X109
/L. Erythrocyte transfusion
was performed in both groups in order to establish the
hemoglobin level over 8 g/dl. All blood products were
transfused after irradiation with 2500 cGy dose.
Evaluation criteria: Neutrophil count over or equal
1X109/L for three consecutive days was considered as
neutrophil engraftment achievement. The length of
time from the reinfusion day to neutrophil engraftment
was assessed as neutrophil engraftment period. Platelet
count over 50X109
/L not requiring platelet transfusion
was also assessed as platelet engraftment achievement.
Days with fever were calculated according to a degree of
fever over 38.1 °C. The length of time from the reinfusion of stem cells to discharge was assessed as hospitalization period. The erythrocyte or platelet transfusion
needs were defined as units.
Statistical analysis: Kolmogorov-Smirnov test was used
to determine the normal distribution variations of the
arithmetic means and standard deviations of numerical
data in the study. When data distribution was out of the
normal distribution variations, Mann-Whitney U test
was used to compare the means of the two groups in
regard to the period between diagnosis and initiation of
transplantation, numbers of pre-transplant chemotherapy courses, total nucleated cells and CD34+ cells
given, days with fever, time to neutrophil and platelet
engraftment and erythrocyte and platelet transfusions.
Chi-square test was used to determine whether any difference was present between the two groups regarding
the percentage of variables of sex and radiation therapy
or not. Fisher's Exact test was used if expected frequency was under 5 or sampling number was under 20. The
means between the two groups regarding the length of
parenteral antibiotic use were compared by t-test.
Statistical analyses were done with SPSS packet program for Windows, version 9.0, SPSS Inc. USA).
P<0.05 level was accepted as statistically significant.
Other values in the article were given as means±standard deviation.
Results
Patients: The mean age of patients not receving GCSF and receiving G-CSF was 37±12.22 years and
32.5±12.72 years, respectively. No statistically significant differences were found in terms of age, sex, pretransplant radiotherapy, previous chemotherapy courses
and time to transplantation from diagnosis between the
two groups (Table I).
Apheresis results: A total of forty two apheresis were
done in two groups. In the group without G-CSF, single apheresis was done in all 15 patients, while in GCSF receiving group, double apheresis was done in 4
patients and single apheresis was done in the remaining
23 patients. At least 2X106 CD34+ stem cells per kilogram were collected finally by apheresis from each
patient. No statistically significant differences were
detected between the two groups regarding TNC and
CD34+ cell counts (TNC= 14.56±7.55X108
/kg vs
12.34±4.46X108
/kg; p=0.65, and CD34+= 9.30±
7.83X106
/kg vs 6.23±3.93X106
/kg; p=0.25) (Tables
I,II,III).
Table I. Patient characteristics
______________________________________________________
G-CSF G-CSF p
Characteristics (day +5) (-) value
______________________________________________________
Number 27 15
Sex (M/F) 16/11 9/6 0.963
Age (mean) 32.50±12.72 37.0±12.22 0.133
Diagnosis
Solid tumor 18 8
Breast cancer 8 4
Osteosarcoma 2 2
Testicular cancer 4 2
Ewing sarcoma 2 0
Primitive
neuroectodermal tumor 1 0
Extragonadal germ cell tumor 1 0
Hematological malignancies
Hodgkin's disease 4 4
Non-Hodgkin lymphoma 4 2
Multiple myeloma 1 1
Pre-transplant radiotherapy 10 5 0.810
Previous chemotherapy
courses (mean) 8.0±5.02 8.45±6.30 0.979
Conditioning regimen
ICE 10 4
L-PAM 0 1
BEAM 5 6
TCM 1 0
CNV 7 4
Alkeran 1 0
CyEAM 1 0
TBI + Cy 2 0
Time to transplantation
from diagnosis (days) (mean)546.92±536.94 906.27±150.51 0.850
TNC (X 10
8
/kg) (mean) 12.34±4.46 14.56±7.55 0.65
CD 34+ cell number (mean) 6.23±3.93 9.30±7.83 0.25
______________________________________________________
Abbreviations: TBI: Total body irradiation, ICE: Ifosfamid,
Carboplatin, Etoposide, L-PAM: Melphalan, BEAM: BCNU,
Etoposide, Ara-C, Melphalan, TCM: Thiotepa, Carboplatin,
Melphalan, CNV: Cyclophosphamide, Mitoxantrone, Etoposide,
CyEAM: Cyclophosphamide, Etoposîde, Ara-C, Melphalan,
TBI+Cy: Total body irradiation, Cyclophosphamide160 · Eylül 2007 · Gülhane TD Arpacý et al.
Table II. Patient characteristics in the group not receiving G-CSF
__________________________________________________________________________________________________________________
Days Days Erythrocyte Platelet Previous
No Age Sex Diagnosis with with suspension suspension Hospitaliz. TNC CD34 cells Conditioning Neutrophil Platelet chemothe. Previous Leukaphfever antib. transf. transf. period (x10
6
/kg) (x10
6
/kg) regimen engraftment engraft. courses RT heresis
__________________________________________________________________________________________________________________________________________
1 35 F Hodgkin’s 2 8 2 1 15 31.67 31.67 BEAM 15 16 8 1
2 26 M Hodgkin’s 6 7 5 4 10 14.8 3.7 BEAM 10 10 5 1
3 24 M NHL 6 7 4 0 12 11.05 3.86 BEAM 12 13 11 1
4 28 M Hodgkin’s 5 14 2 1 14 8.96 8.06 BEAM 12 16 24 + 1
5 49 M NHL 5 9 4 1 10 9.94 4.97 BEAM 10 10 6 + 1
6 51 F M.myeloma 1 12 2 1 15 9 2.25 L-PAM 12 20 6 + 1
7 50 M Hodgkin’s 4 12 2 2 12 18.37 11.76 BEAM 11 12 8 + 1
8 25 M Osteosarcoma 0 10 4 1 12 8.33 2.45 ICE 12 12 21 + 1
9 49 F Breast cancer 7 13 3 1 13 19.87 19.87 CNV 7 7 4 1
10 22 M Osteosarcoma 7 11 2 1 11 8.53 11.85 ICE 11 10 2 1
11 29 M Testic. cancer 9 15 3 1 15 7.2 3.3 ICE 14 11 10 1
12 48 F Breast cancer 10 17 3 0 15 11.28 5.98 CNV 11 12 4 1
13 45 F Breast cancer 5 20 4 2 20 10.6 10.1 CNV 20 21 4 1
14 42 F Breast cancer 7 14 2 1 14 27.28 7.9 CNV 10 15 4 1
15 32 M Testic. cancer 1 9 2 2 15 21.5 11.76 ICE 12 16 10 1
__________________________________________________________________________________________________________________________________________
Abbreviations : TNC: Total nucleated cells, RT: Radiotherapy, NHL: non-Hodgkin lymphoma; BEAM: BCNU, Etoposide, Ara-C, Melphalan; ICE: Ifosfamid,
Carboplatin, Etoposide; CNV: Cyclophosphamide, Mitoxantrone, Etoposide, L-PAM: Melphalan.
Table III. Patient characteristics in the group receiving G-CSF on day +5
__________________________________________________________________________________________________________________
Days Days Erythrocyte Platelet Previous
No Age Sex Diagnosis with with suspension suspension Days TNC CD34 cellsConditioning Neutrophil Platelet chemothe. PreviousLeukaphfever antibiotic (units) (units) Hospitaliz. (x10
8
/kg)(x10
6
/kg) regimen engraft. engraft. courses RT heresis
______________________________________________________________________________________________________________________________________________
1 46 F Breast ca. 5 9 2 0 13 12.20 3.78 TCM 10 8 4 1
2 56 M NHL 1 4 2 1 15 11.08 1.10 BEAM 13 11 17 + 1
3 21 M NHL 3 5 0 0 10 16.04 7.37 TBI+Cy 10 12 5 1
4 30 F Breast ca. 4 7 0 0 10 9.50 9.50 CNV 10 10 8 1
5 21 M Osteosar. 3 5 2 0 12 21.86 14.21 ICE 9 11 2 1
6 28 F Breast ca. 1 5 0 0 14 10.78 6.14 CNV 13 11 6 1
7 52 F M.myelo. 6 17 7 2 35 7.88 5.51 ALKERAN 10 15 4 + 1
8 46 M Testicu.ca. 1 8 1 1 14 8.47 0.84 ICE 11 14 9 2
9 21 M Osteosar. 6 9 4 2 10 12.10 5.56 ICE 9 11 2 1
10 23 M Testicu.ca. 3 7 4 1 14 17.69 1.95 ICE 11 20 6 + 2
11 22 M Hodgkin’s 2 4 2 0 10 14.26 10.12 CyEAM 8 12 8 1
12 23 M Hodgkin’s 1 4 2 0 11 16.60 8.46 BEAM 10 10 9 + 1
13 56 F Breast ca. 4 8 4 0 10 15.52 6.51 CNV 10 10 4 1
14 22 M Extrago.tm. 5 7 6 1 14 8.70 5.39 ICE 11 12 5 1
15 24 M PNET 5 6 0 1 11 9.25 3.88 ICE 9 10 5 + 1
16 23 F Hodgkin’s 0 0 2 0 12 13.23 4.10 BEAM 11 14 23 + 1
17 29 F Breast ca. 2 9 3 0 14 9.87 2.36 CNV 12 13 10 + 1
18 19 F NHL 3 7 2 0 12 9.00 2.00 BEAM 11 18 12 + 2
19 28 F Breast ca. 3 10 0 1 14 19.55 2.70 CNV 11 13 7 1
20 23 M NHL 6 10 0 0 13 5.52 7.39 TBI+Cy 11 12 4 1
21 35 M Hodgkin’s 1 6 2 0 14 9.90 13.20 BEAM 11 15 14 + 1
22 52 F Breast ca. 4 7 2 0 12 12.20 10.37 CNV 11 9 4 1
23 42 F Breast ca. 4 8 2 0 12 6.29 11.90 CNV 10 9 4 1
24 21 M Ewing sarc. 0 0 2 0 8 13.20 8.05 ICE 10 11 16 + 1
25 46 M Ewing sarc. 3 7 2 1 13 6.50 1.95 ICE 9 10 6 1
26 46 M Testicu. tm. 13 13 4 2 17 14.62 2.03 ICE 12 13 12 2
27 23 M Testicu. tm. 1 9 2 2 15 21.50 11.76 ICE 12 16 10 1
__________________________________________________________________________________________________________________________________________
Abbreviations : NHL: Non-Hodgkin lymphoma ; BEAM: BCNU, Etoposide, Ara-C, Melphalan; ICE: Ifosfamide, Carboplatin, Etoposide; CNV: Cyclophosphamide,
Mitoxantrone, Etoposide, PNET: Primitive Neuroectodermal Tumor, TCM: Thiotepa, Carboplatin, Melphalan, TBI+CV: Total Body Irradiation, Cyclophosphamide,
CVEAM: Cyclophosphamide, Etoposide, Ara-C, MelphalanCilt 49 · Sayý 3 · Gülhane TD G-CSF on post-transplant +5th day · 161
Neutrophil and platelet engraftment: In patients receiving
and not receiving G-CSF, neutrophil engraftment was
achieved on days 10.55±1.21 and 11.93±2.89, respectively. In the first group with G-CSF, the engraftment
was faster than the other group, revealing a statistical
significance (p=0.04). Furthermore, in patients receiving and not receiving G-CSF, platelet engraftment was
achieved on days 12.22±2.79 and 13.40±3.89, respectively. Two groups revealed no statistically significant
differences for platelet engraftment (p=0.31) (Table
IV).
Supportive care findings: Number of days with fever
and days requiring antibiotic treatment were significantly lower in G-CSF receiving group than without
G-CSF group with 3.33±2.66 vs 5±2.95 days; p=0.03
and 7.07±3.46 vs 11.87±3.74 days; p<0.001, respectively.
Post-transplant erythrocyte suspension transfusion
need was similar in both groups (2.18±1.78 vs
2.93±1.03 units; p=0.05); however, platelet suspension
transfusion need was lower in G-CSF receiving group
in post-transplant period (0.56±0.75 vs 1.27±0.96
units; p=0.01).
The length of hospitalization after the completion of
transplantation was similar in both groups (13.30±4.79
days in G-CSF receiving group vs 13.53±2.56 days in
the group not receiving G-CSF; p=0.26) (Table IV).
Discussion
Although some studies reveal no benefit of growth
factors for neutrophil engraftment, many others suggest
that hematopoietic growth factors accelerate neutrophil
engraftment, shorten number of days with fever and
antibiotic use (1-7). In our study, we aimed to compare
the two groups receiving and not receiving G-CSF in
post-transplant period and analyzed the results of
engraftment as well as supportive needs between the
two groups.
Ojeda et al. randomized 62 patients with advanced
stage breast cancer, lymphoma and acute myeloid
leukemia into two groups. One group received G-CSF
from day +5 after the transplantation and the other
group received no growth factors (13). They reported
that the neutrophil engraftment was faster in G-CSF
receiving group (12 days vs 10 days, p=0.0008); however, platelet engraftment was not changed (p=0.11) and
no significant difference was noted between the groups
regarding days with fever, number of infections and
supportive care requirements.
Azevedo et al. randomized 87 patients into two
groups in a multicenter study. In one group they gave
G-CSF on 5 µg/kg/day dose from the first day after the
transplantation and in the second group they started the
same dose of G-CSF on the 5th day after the infusion
until neutrophil engraftment (14). The period with
neutropenia was shorter in patients who received GCSF starting on the first day. No significance was noted
in Azevedo's study between the two groups regarding
either the neutrophil and platelet engraftment time and
days with fever.
On the other hand, Hornedo et al. investigated the
role of post-transplant G-CSF administration in breast
cancer cases (15). They randomized the patients into
three groups. They gave G-CSF at 5 µg/kg/day dose on
the 0th day to the first group and on the 5th day to the
second group, whereas the third group has received no
growth factor. When compared, neutrophil engraftment
was achieved earlier in growth factor supported group
(p=0.001). The extent of hospitalization was relatively
shorter in patients who received G-CSF. Although neutrophil engraftment was achieved earlier in the first
group than in the second group, days with fever, hospitalization duration, platelet engraftment, erythrocyte or
platelet requirements were found statistically insignificant. In fact, the investigators have recommended
administering G-CSF on day +5 as a standard practice.
We revealed in the current study that neutrophil
engraftment was faster in G-CSF administered patients
on day +5 in post-transplant period. Our findings are
consistent with the results of the study of Ojeda et al. in
terms of neutrophil engraftment (11.93±2.89 vs
10.55±1.21 days; p=0.04) and platelet engraftment
Table IV. Engraftment and supportive care findings
__________________________________________________________________________________________________________________
Clinical parameters G-CSF (-) G-CSF (day +5) p value
__________________________________________________________________________________________________________________
Neutrophil engraftment (1X10
9
/L) 11.93±2.89 10.55±1.21 0.04
Platelet engraftment (50X10
9
/L) 13.40±3.89 12.22±2.79 0.31
Days with fever (>38.1ºC) 5.0±2.95 3.33±2.66 0.03
Days with antibiotics 11.87±3.74 7.07±3.46 <0.001
Erythrocyte suspension transfusion (units) 2.93±1.03 2.18±1.78 0.05
Platelet suspension transfusion (units) 1.27±0.96 0.56±0.75 0.01
Post-transplant hospitalization (days) 13.53±2.56 13.30±4.79 0.26
__________________________________________________________________________________________________________________162 · Eylül 2007 · Gülhane TD Arpacý et al.
(13.40±3.89 vs 12.22±2.79 days; p=0.315). Significant
decrease in days with fever and antibiotic use in our
study may result from early neutrophil engraftment
achievement. On the other hand, platelet engraftment
was similar in both groups (13.40 vs 12.22 days;
p=0.31). Patients required more platelet transfusion in
the group not administered G-CSF compared with the
group given G-CSF (1.27 vs 0.56; p=0.01), which may
be due to the threshold accepted for platelet transfusion
to be 20X109
/L in the first (without G-CSF support)
than the other group where the threshold for trombopheresis was set to be 10X109
/L.
In conclusion, we suggest that cases undergoing
PBSCT with CD34+ cell number over or equal to
2x106
/kg and with G-CSF support on day +5 have
faster neutrophil engraftment, shorter period of days
with fever and also antibiotic use. Nevertheless, our
findings as regards of hospitalization duration, erythrocyte and platelet transfusion requirements are similar in
both G-CSF supported and not supported groups. In
fact, starting G-CSF administration on day +5 will
therefore reduce post-transplant cost due to the growth
factor use and seems therefore to be a rational approach.

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