Peripheral blood stem cell mobilization in multiple myeloma: Growth factors or chemotherapy?

Table 1 Growth factor mobilization

Ref.	Disease	Collection strategy	n	CD34+ yield (× 10-6 cell/kg): Median (range)	Failure n (%)
Desikan et al[26]	MM	G-CSF 10-16 μg/kg per day	117	6.2 (0.6-34.1)	NR
Kröger et al[27]	MM	G-CSF 10-24 μg/kg per day	25	3.8 (0.3-17)	3 (12)
Popat et al[31]	MM	G-CSF	302	NR	9%
Pusic et al[90]	MM	G-CSF 10 μg/kg per day	384	4.6	24 (6.3)
	NHL HD	G + C	17	8.5	1 (5.9)
Weaver et al[34]	BC	G-CSF 10 μg/kg per day	14	0.6 (0.1-2.8)	NR
		G-CSF 20 μg/kg per day	13	1 (0.2-5.2)
		G-CSF 30 μg/kg per day	14	2.4 (0.6-6.8)
		G-CSF 40 μg/kg per day	14	1.4 (0.1-4.8)
Weisdorf et al[42]	NHL	GM-CSF 250 μg/m2 per day	16	4.78 (3.02-10.68)	0
	HD	G-CSF 250 μg/m2 per day	15	8.01 (3.17-29)	0
Spitzer et [41]	BC GCT	GCSF 10 mcg/kg per day	26	21.45 (1.63-182.91)	NR
	NHL HD	GCSF 10 mcg/kg per day +	24	13.33 (0.56-102.08)
	MM	GM-CSF 5 mcg/kg per day
Hosing et al[39]	MM	PEG 12 mg × 1	19	8.4 (4.1-15.8)	0
		G-CSF 10 μg/kg per day	8	8.1 (5.17-19.2)	0

MM: Multiple myeloma; G-CSF: Granulocyte colony stimulating factor; NR: Not reported; BC: Breast cancer; NHL: Non-hodgkin’s lymphoma; GM-CSF: Granulocyte macrophage colony stimulating factor; HD: Hodgkin’s disease; GCT: Germ cell tumor; PEG: Pegylated filgrastim.

Table 2 Growth factors following chemotherapy

Ref.	Disease	Collection strategy	n	CD34+ yield (× 10-6 cell/kg): Median (range)	Failure rates n (%)
Weaver et al[91]	MM ML BC	G-CSF 6 μg/kg per day	49	12 (0.1-54)	2 (4.1)
		GM-CSF 250 μg/m2 per day	49	5.4 (0.02-64)	4 (8.2)
		GM-CSF × 5 d then G-CSF 6 μg/kg per day	52	10.5 (0.4-96)	1 (1.9)
Arora et al[43]	MM	G-CSF 250 μg/m2 per day	35	16.4 (1.1-71.7)	NR
		GM-CSF 250 μg/m2 per day	37	12.8 (0.4-94.5)
Tricot et al[46]	MM	PEG 6 mg q7d × 2	97	NR; no difference	NR
		G-CSF 10 μg/kg per day	140
Fruehauf et al[92]	MM	PEG 12 mg × 1	26	9.7 (4.9-40.5)	3 (11.5)
Steidl et al[93]	MM	PEG 12 mg × 1	12	7.4 (4.9-38)	0
		G-CSF 8.5 μg/kg per day	12	10.8 (5-87)	0

MM: Multiple myeloma; ML: Malignant lymphoma; BC: Breast cancer; G-CSF: Granulocyte colony stimulating factor; GM-CSF: Granulocyte macrophage colony stimulating factor; NR: Not reported; NHL: Non-hodgkin’s lymphoma; PEG: Pegylated filgrastim.

Table 3 Impact of chemotherapy on cell yield and morbidity

Ref.	Collection strategy	n	CD34+ yield (× 10-6 cell/kg): median (range)	Hospital days: median (range)	Infection (%)	Transfusions (%) platelet/PRBC
Desikan et al[32]	CY 6 g/m2 + G-CSF 6 μg/kg per day	22	33.4 (NR)	No difference	18	86/86
	G-CSF 16 μg/kg per day	22	5.8 (NR)		0	18/55
Alegre et al[51]	CY 4 g/m2 + GM-CSF	18	6.8 (1.8-34.8)	21 (16-34)	11	33.3/27.7
	G-CSF 10 μg/kg per day	22	4.85 (2.1-10.05)	0	0	0/0
Fitoussi et al[60]	CY 7 g/m2 + HGF	74	8.6 (0.4-166)	15 (9-34)	17.6	75.7/94.6
	CY 4 g/m2 + HGF	42	13.4 (0.7-66.8)	22 (13-55)	16.7	26.2/52.4
Jantunen et al[61]	CY 4 g/m2 + G-CSF 5-10 μg/kg per day	32	4.9 (0.8-47.4)1	9 (6-14)	NR	34/53
	CY 1.2-2 g/m2 + G-CSF 5 μg/kg per day	42	5.6 (0.9-19)1	5 (3-12)	NR	0/28
Gojo et al[65]	CY 4.5 g/m2 + G-CSF	28	21.38 (0-106.8)	8 (4-24)	25	57/NR
	CY 4.5 g/m2 + VP-16 + G-CSF	49	22.39 (0-114.71)	7 (3-68)	53	67/NR
Hamadani et al[94]	CY 3-4 g/m2 + G-CSF	55	16.6 (2-82)	4 (1-9)	NR	21.8/34.5
	CY 1.5 g/m2 + G-CSF	68	7.5 (0-18)	3 (1-5)	NR	2.9/8.8
Hiwase et al[95]	CY 3-4 g/m2 + G-CSF	26	7.71	7 (3-22)	19	No difference
	CY 1-2 2 g/m2 + G-CSF	61	5.17	6 (3-18)	5

¹1st apheresis session. PRBC: Packed red blood cells; CY: Cyclophosphamide; G-CSF: Granulocyte colony stimulating factor; NR: Not reported; HGF: Hematopoietic growth factor; VP-16: Etoposide.

Table 4 International Myeloma Working Group Consensus guidelines and recommendations on mobilization in malignant lymphoma[20]

Strategy	Recommendations
Mobilization
G-CSF alone	Limit use to patients
	Treated with ≤ 1 line of therapy
	Never exposed to melphalan
	Received ≤ 4 cycles of lenalidomide
	Use doses from 10-16 μg/kg per day
	Monitor PB CD34+ count
Chemomobilization + G-CSF	Limit to patients who have not adequately responded to salvage therapy
Plerixafor	Suitable for all patients particularly if goals include
	Highest cell yield obtainable
	Fewer apheresis sessions
Remobilization
Plerixafor	P + G-CSF or P + CM + G-CSF
Chemomobilization	Acceptable in patients who failed cytokine mobilization
Bone marrow harvest	Use as third-line option in patients in whom ASCT is compelling

PBCD34⁺: Peripheral blood CD34⁺ cells; P + G-CSF: Plerixafor + granulocyte colony stimulating factor; P + CM + G-CSF: Plerixafor + chemomobilization + granulocyte colony stimulating factor.

Table 5 Advantages and disadvantages of mobilization strategies

Mobilization strategy	Advantages	Disadvantages
Growth factor	Cost effective	No anti-myeloma effect
	Successful mobilization in most patients	Multiple injections and collections
	Predictable schedule	Potential sub-optimal yield
CM	Anti-myeloma effect	Cytopenias
	Increased cell yield	Infection risk
	Fewer apheresis sessions	Hospital admission
		Potential transfusion requirement
		Unpredictable count recovery
Plerixafor	Rapid kinetics	Higher drug cost
	Increased cell yield
	Fewer apheresis sessions

CM: Chemomobilization.