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Table 1 The characteristics and mobilization results of the 44 studies included in review

From: Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis of randomized controlled trials

References

Study design

Enroll period

Patients

Mobilization regimen

Main results

G-CSF plus Plerixafor SD versus G-CSF alone

DiPersio et al. [32]

Phase 3 RCT, double-blind, multicenter

Jan. 2005–Aug. 2006

NHL

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed significantly higher rate of achieving optimal target (P < 0.001)* and higher CD34+ cells collected

DiPersio et al. [33]

Phase 3 RCT, double-blind, multicenter

Feb. 2005–Jul. 2006

MM

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed significantly higher rate of achieving optimal target (P < 0.001)* and higher CD34+ cells collected

Matsue et al. [48]

Phase 2 RCT, open-label, multicenter

Nov. 2014–Mar. 2016

NHL

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed higher rate of achieving optimal target

Nahi et al. [50]

Phase 2 RCT, open-label, multicenter

NA

MM

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed higher CD34+ cells yield

Ri et al. [55]

Phase 2 RCT, open-label, multicenter

Oct. 2014–Jul. 2015

MM

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed higher rate of achieving optimal target

Zhu et al. [66]

Phase 3 RCT, double-blind, multicenter

Apr. 2013–Nov. 2014

NHL

G-CSF SD; G-CSF SD + Plerixafor SD

The Plerixafor group showed significantly higher rate of achieving optimal target (P < 0.0001)*

G-CSF plus YF-H-2015005 versus G-CSF alone

Liu et al. [44]

Phase 3 RCT, double-blind, multicenter

Jan. 2017- Dec. 2018

NHL

G-CSF SD; G-CSF SD + YF-H-2015005

YF-H-2015005 significantly increased the rate of achieving optimal target (P < 0.001)* and the number of CD34+ cells collected (P < 0.001)*

Chemotherapy regimens plus G-CSF versus G-CSF alone

Karanth et al. [40]

RCT, open-label, single center

Nov. 1998–Nov. 2002

HL, NHL, MM or CLL

G-CSF SD; CY + G-CSF RD

No significant differences in rate of successful mobilization (P = 0.21) and the number of CD34+ cells collected

Silvennoinen et al. [58]

Phase 2 RCT, multicenter

Jan. 2013- Feb. 2015

MM

G-CSF SD; CY + G-CSF RD

CY plus G-CSF RD resulted in significantly higher CD34+ cells yield (P = 0.012)*

Valtola et al. [61]

RCT, multicenter

Jan. 2013–Nov. 2014

MM

G-CSF SD; CY + G-CSF RD

No significant differences in the number of total CD34+ cells collected (P = 0.064)

Milone et al. [49]

RCT, single center

Mar. 1998–Jul. 2002

NHL or HL

G-CSF SD; CY + G-CSF SD

No significant differences in the number of CD34+ cells collected (P > 0.9) and the rate of successful mobilization (P > 0.4)

Narayanasami et al. [51]

RCT, single center

Nov. 1997–Nov. 2000

NHL or HL

G-CSF SD; CY + G-CSF SD

CY plus G-CSF SD resulted in significantly higher total number of CD34 + cells collected (P = 0.004*)

Czerw et al. [30]

Phase 3 RCT, open-label, single center

Mar. 2013–Mar. 2016

MM

G-CSF SD; ID-AraC + G-CSF SD

The ID-AraC group showed significantly higher total number of CD34+ cells collected (P < 0.000001) and higher rate of reaching optimal target (P = 0.0003)*

Comprisons among chemotherapy regimens

Chen et al. [28]

RCT, single center

Jan. 2005–May 2010

NHL

CY + G-CSF RD; MA + G-CSF RD

The number of total CD34+ cells collected were similar (P = 0.117)

Pavone et al. [54]

RCT, single center

NA

NHL

CY + G-CSF RD; DHAP + G-CSF RD

No significant differences in the mean number of CD34+ cells collected

Vela-Ojeda et al. [62]

RCT, single center

Aug. 1994–Jun. 1999

NHL, HL or MM

CY + GM-CSF RD; Ifosfamide + GM-CSF RD

No significant differences in the number of CD34+ cells collected (P = 0.1)

Jeker et al. [38]

Phase 2 RCT, single center

Dec. 2013–Apr. 2017

MM

Vinorelbine + G-CSF SD; Gemcitabine + G-CSF SD

The CD34+ cell yield was significantly higher in the Vinorelbine group (P = 0.001)*

Weaver et al. [63]

RCT, single center

Sept. 1992–Aug. 1994

NHL or HL

CE + G-CSF RD; CEP + G-CSF RD

No significant difference in the number of total CD34+ cells collected (P = 0.09)

Zhang et al. [64]

RCT, single center

Jan. 2001–Oct. 2012

NHL

MEOD + G-CSF SD; MEOD + MTX + G-CSF SD

The MTX group showed significantly higher CD34+ cells yield (P < 0.05)*

Pegfilgrastim versus G-CSF

Bouko et al. [26]

Phase 2 RCT

May 2006–Nov. 2011

MM

G-CSF SD; Pegfilgrastim 12 or 18 mg

No significant differences in the rate of reaching minimal and optimal target

Kuan et al. [42]

RCT, triple blinded, single center

Sep. 2010–Dec. 2012

Acute leukemia, MM or lymphoma

CY + G-CSF RD; CY + Pegfilgrastim 6 mg on day 3 or day 7

Pegfilgrastim 6 mg on day 7 produced highest rate of successful mobilization

Russell et al. [56]

Phase 2 RCT, double-blind, multicenter

Feb. 2003–Sep. 2004

NHL

ICE + G-CSF RD; ICE + Pegfilgrastim 6 mg or 12 mg

No significant differences in the number of CD34+ cells collected and the rate of reaching optimal target

Skopec et al. [59]

RCT, single center

Feb. 2012–Nov. 2014

MM

G-CSF SD; Pegfilgrastim 12 mg

No significant difference in the number of CD34+ cells collected (P = 0.428)

Biosimilar G-CSF versus G-CSF

Bhamidipati et al. [25]

Phase 2 RCT, open-label, single center

Aug. 2014–Jun. 2016

MM or NHL

G-CSF SD + Plerixafor SD; Biosimilar G-CSF (Tbo-filgrastim) + Plerixafor SD

No significant differences in the number of CD34+ cells collected on day 5 (P = 0.873) and successful rate of reaching optimal target (P = 0.916)

Manko et al. [46]

RCT, single center

Jun. 2010–Sep. 2011

MM, NHL, HL, AML or other

Chemotherapy + G-CSF SD; Chemotherapy + Biosimilar G-CSF SD;

No significant differences in the number of CD34 + cells collected and the rate of successful mobilization

Marchesi et al. [47]

RCT, single center

Oct. 2014–Nov. 2017

NHL or HL

Chemotherapy + G-CSF RD; Chemotherapy + Biosimilar G-CSF SD

No significant differences in the number of CD34+ cells collected (P = 0.805) and the rate of achieving optimal target (P = 1.00)

GM-CSF versus G-CSF

Arora et al. [24]

RCT, single center

1993–2002

MM

CMD + G-CSF RD; CMD + GM-CSF RD

Two group showed similar CD34+ cells collection (P = 0.8). G-CSF is associated with faster neutrophil and platelet recovery

Demuynck et al. [31]

RCT, single center

NA

MM

CY + G-CSF SD; CY + GM-CSF SD

No significant difference in CD34+ cells yield (P = 0.27). GM-CSF is associated with increased toxicity

Gazitt et al. [35]

RCT, single center

May 1997–Mar. 2000

NHL

CY + G-CSF SD; CY + GM-CSF RD; CY + GM-CSF RD + G-CSF SD

No significant differences in successful rate of collecting ≥ 2 × 106 CD34+CD45dim cells/kg

Hohaus et al. [37]

RCT, double-blind, single center

Aug. 1992–Dec. 1994

HL

G-CSF RD; GM-CSF RD

No significant differences in the number of CD34+ cells collected (P = 0.696)

SCF versus no SCF

Bourin et al. [27]

RCT, single center

NA

MM

CY + G-CSF RD; SCF + G-CSF SD

The total number of CD34+ cells collected were similar

Facon et al. [34]

RCT, open-label, multicenter

Mar. 1996–Oct. 1997

MM

CY + G-CSF RD; CY + SCF + G-CSF RD

The SCF group showed significant higher CD34+ cells yield (P = 0.007)*

Johnsen et al. [39]

Phase 2 RCT, open-label, multicenter

NA

Malignant lymphoma

CY + G-CSF SD; SCF + G-CSF SD

The CY plus G-CSF group showed higher number of CD34+ cells collected and higher rate of reaching optimal target on first leukapheresis (P = 0.00018)*

Stiff et al. [60]

RCT, multicenter

NA

NHL or HL

G-CSF SD; SCF + G-CSF SD

SCF group showed an increase in the median total CD34+ cells collected (P = 0.05)

Addition of other cytokines

Hart et al. [36]

RCT, single center

May 2004–Jan 2006

MM

IEV + G-CSF RD; IEV + G-CSF RD + EPO

No significant differences in the number of CD34+ cells collected (P = 0.57)

Lonial et al. [45]

RCT, single center

NA

Lymphoma or MM

Chemotherapy + G-CSF SD; Chemotherapy + G-CSF RD + GM-CSF RD

No significant differences in the number of CD34+ cells collected

Zhu et al. [65]

RCT, single center

2002–2005

NHL or AML

Chemotherapy + G-CSF RD; Chemotherapy + G-CSF RD + IL-11

No significant differences in the number of total CD34+ cells collected

Zhu et al. [67]

RCT, multicenter

NA

NHL

CE + G-CSF RD; CE + G-CSF RD + TPO

The TPO group showed significantly higher total number of CD34+ cells collected (P = 0.0054) and higher rate of reaching optimal target (P = 0.021)*

Comparison of different administration schedules

Kim et al. [41]

RCT, single center

Jun. 2003–Oct. 2004

MM or NHL

CY or ESHAP (± Rituximab) + G-CSF SD (single-dose versus split-dose)

No significant differences in the number of CD34+ cells collected (P = 0.47) and rate of reaching optimal target (P = 0.24)

Kuruvilla et al. [43]

Phase 4 RCT, open-label, multicenter

Oct. 2010–Feb. 2013

NHL

G-CSF SD + Plerixafor SD; G-CSF SD + Plerixafor FD

No significant differences in the rate of achieving optimal target (P = 0.395)

Ozcelik et al. [53]

RCT, single center

2005–2008

NHL or MM

CE + G-CSF SD (early versus late)

No significant differences in the number of CD34+ cells collected (P = 0.781)

Samaras et al. [57]

Phase 2 RCT, single center

2011–2016

MM

Vinorelbine + G-CSF SD; Vinorelbine + G-CSF RD

No significant differences in the number of CD34+ cells collected (P = 0.99)

Others

     

Copelan et al. [29]

RCT, single center

May. 2000–Apr. 2005

B-cell NHL

VP-16 + G-CSF SD; Rituximab + VP-16 + G-CSF SD

The Rituximab group showed significantly higher total number of CD34 + cells collected (P = 0.021)*

Orciuolo et al. [52]

RCT, open-label, multicenter

Apr. 2005–Jul. 2009

MM

CY + G-CSF SD (lenograstim versus filgrastim)

No significant differences in the rate of reaching optimal target

  1. AML, acute myelocytic leukemia; CE, cyclophosphamide and etoposide; CEP, cyclophosphamide and etoposide plus cisplatin; CLL, chronic lymphocytic leukemia; CMD, cyclophosphamide, mitoxantrone and dexamethasone; CY, cyclophosphamide; DHAP, dexamethasone, high-dose cytarabine, and cisplatin; ESHAP, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin; EPO, erythropoietin; FD, fixed dose; GM-CSF, granulocyte–macrophage colony-stimulating factor; G-CSF: granulocyte colony-stimulating factor; HL, Hodgkin lymphoma; ICE, ifosfamide, carboplatin and etoposide; ID-AraC, intermediate-dose cytarabine; IEV, ifosfamide, epirubicin and etoposide; IL-11, interleukin 11; MA, methotrexate, cytarabine; MEOD, mitoxantrone, etoposide, vindesine and dexamethasone; MM, multiple myeloma; MTX, methotrexate; NA, not available; NHL, non-Hodgkin lymphoma; RCT, randomized controlled trial; RD, reduced dose; SCF, stem cell factor; SD, standard dose; TPO, thrombopoietin; VP-16, etoposide; YF-H-2015005, a new CXCR4 antagonist
  2. *Results with significant difference