Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?

Crusoe, Edvan de Queiroz; Higashi, Fabiana; Martinez, Gracia Aparecida; Barros, José Carlos; Bellesso, Marcelo; Rossato, Marina; Marret, Ana Cinira F.; Chiattone, Carlos Sérgio; Hungria, Vania Tietsch de Moraes

doi:10.1016/j.bjhh.2016.06.004

Acessibilidade / Reportar erro

Brasil

Revista Brasileira de Hematologia e Hemoterapia

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original Articles • Rev. Bras. Hematol. Hemoter. 38 (4) • Oct-Dec 2016 • https://doi.org/10.1016/j.bjhh.2016.06.004 copy

Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background:

Cyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 10⁶ CD34⁺ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34⁺ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone.

Methods:

A retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100-200 mg/day, respectively. Mobilization doses were 10-15 mcg/kg granulocyte-colony stimulating factor with 2-4 g/m² cyclophosphamide, or 15-20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 10⁶ CD34⁺ cells/kg was considered sufficient.

Results:

Eighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51-62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected.

Conclusion:

The number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34⁺ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.

Keywords:
Bone marrow transplantation; Multiple myeloma; Granulocyte-colony stimulating factor; Cyclophosphamide

Variables	G-CSF	G-CSF plus Cyclophosphamide	p-Value
Age at start of treatment - years
n	80	18
Range	36-69	42-68	0.933
Mean ± SD	56.2 ± 7.3	56.4 ± 6.5
Median (IQR)	58 (53-61)	56.5 (54-60)

Gender - n (%)
n	80	18
Female	31 (44.3)	5 (27.8)	0.284
Male	39 (55.7)	13 (72.2)

Ig subtype - n (%)
n	80	18
IgG K/L	30 (42.8)	9 (50)	NS
IgA K/L	9 (12.8)	4 (22.2)
Light	7 (10)	4 (22.2)
Other/not analyzed	24 (34.2)	1 (5.6)

Performance status - n (%)
n	44	14
0	19 (43.2)	7 (50.0)	0.944
1	8 (18.2)	2 (14.3)
2	11 (25.0)	4 (28.6)
3	5 (11.4)	1 (7.1)
4	1 (2.3)	0

Osseous lesion - n (%)
n	39	6
No	8 (20.5)	5 (83.3)	0.005
Yes	31 (79.5)	1 (16.7)

DSS - n (%)
n	70	18
IIA	7 (10.0)	1 (5.6)	0.769
IIIA	53 (75.7)	15 (83.3)
IIIB	10 (14.3)	2 (11.1)

ISS - n (%)
n	68	17
1	23 (33.8)	4 (23.5)	0.678
2	29 (42.7)	9 (52.9)
3	16 (23.5)	4 (23.5)

Variable	G-CSF	G-CSF plus Cyclophosphamide	p-Value
Hemoglobin - g/dL
n	66	18
Mean ± SD	9.6 ± 2.5	9.7 ± 1.6	0.972

Creatinine - mg/dL
n	54	18
Mean ± SD	1.2 ± 0.8	1.5 ± 1.4	0.443
Median (IQR)	0.9 (0.7-1.5)	1.05 (0.8-1.5)

Total calcium - mg/dL
n	49	18
Mean ± SD	9.9 ± 1.6	10.2 ± 1.7	0.099
Median (IQR)	9.3 (9.0-10.1)	9.75 (9.6-10.6)

Ionized calcium - mol/L
n	22	17
Mean ± SD	5.6 ± 2.0	5.5 ± 0.7	0.955
Median (IQR)	5.3 (4.9-6.5)	5.3 (5.2-5.6)

β2-microglobulin - mg/L
n	51	17
Mean ± SD	4.3 ± 3.2	7.3 ± 7.1	0.128
Median (IQR)	3.3 (2.2-5.4)	3.8 (3.0-7.5)

C-reactive protein - mg/dL
n	29	15
Mean ± SD	13.6 ± 25.5	22.8 ± 50.2	0.063
Median (IQR)	2.3 (0.4-11.9)	7.2 (3.3-16.2)

LDH - U/L
n	27	18
Mean ± SD	278 ± 193	335 ± 181	0.320

Albumin - g/dL
n	45	18
Mean ± SD	3.6 ± 0.7	3.5 ± 0.6	0.840

M component - g/dL
n	25	18
Mean ± SD	3.6 ± 2.2	4.9 ± 3.1	0.136

Plasmocytes - %
n	55	18
Mean ± SD	40.7 ± 27.0	41.0 ± 32.4	0.960

Variable	G-CSF	G-CSF/Cyclophosphamide	p-Value
Cell count - ×10 ⁶ /kg
n	70	18
Mean ± SD	3.4 ± 1.3	6.4 ± 7.7	0.008
Median (IQR)	3.2 (2.3-3.8)	3.8 (3.1-4.4)

Apheresis - days
n	60	17
Mean ± SD	1.5 ± 0.6	1.2 ± 0.5	0.077
Median (IQR)	1 (1-2)	1 (1-1)

Response type and time point	Response	No response	p-Value
After four cycles ≥ PR
Cell count - ×10⁶/kg	n = 74	n = 14
Mean ± SD	4.2 ± 4.1	3.1 ± 0.8	0.176
Median (IQR)	3.35 (2.7-4.0)	3.15 (2.3-3.3)

Pre-aHSCT ≥ PR
Cell count - ×10⁶/kg	n = 80	n = 8
Mean ± SD	4.1 ± 4.0	3.3 ± 0.8	0.780
Median (IQR)	3.3 (2.6-4.05)	3.3 (2.95-3.55)

After four cycles ≥ VGPR
Cell count - ×10⁶/kg	n = 36	n = 52
Mean ± SD	5.0 ± 5.6	3.4 ± 1.4	0.228
Median (IQR)	3.35 (2.95-5.25)	3.3 (2.35-3.8)

Pre-aHSCT ≥ VGPR
Cell count - ×10⁶/kg	n = 47	n = 41
Mean ± SD	4.6 ± 5.0	3.4 ± 1.5	0.135
Median (IQR)	3.4 (3.025-4.275)	3.2 (2.3-3.825)

Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular R. Dr. Diogo de Faria, 775 cj 114, 04037-002 São Paulo/SP/Brasil, Tel. (55 11) 2369-7767/2338-6764 - São Paulo - SP - Brazil
E-mail: secretaria@rbhh.org

Acompanhe os números deste periódico no seu leitor de RSS

[1] * Corresponding author at: Departamento de Hematologia e Oncologia, Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), Rua Dr. Cesário Motta Jr., 61, 01221-020 São Paulo, SP, Brazil. E-mail address: edvancrusoe@gmail.com (E.Q. Crusoe).