Abstract 4402

Background

High-dose chemotherapy supported by autologous stem cell transplantation is a widely used therapeutic modality especially in patients with non-Hodgkin lymphomas (NHL) and multiple myeloma (MM). However, mobilization failure rates following first attempt are estimated to be between 5% and 30% and remobilization is required in those patients. Although plerixafor, a selective CXCR4 antagonist, is a promising agent for these purpose, mobilization with chemotherapeutic agents would be a hands-on option.°° Therefore we investigated the feasibility of high dose methotrexate and cytarabine with G-CSF as a remobilization regimen in those who failed a prior mobilization and collection with chemotherapy and G-CSF.

Patients and methods

Mobilization failure was defined as a collection of less than 5 × 106 CD34+ cells after 3–5 apheresis procedures. Methotrexate (3,500 mg/m2 in a 120 min infusion) on day 1 and cytarabine (3,000 mg/m2 infusion for 120 min) on day 4 and day 5 were followed by G-CSF. Supportive care and leucovorine rescue were done as standard protocol. Peripheral blood (PB) hematopoietic progenitor cells (HPCs) were counted with the Sysmex SE9000. PB progenitor cell harvest was initiated when HPC levels reached at least 5 per mm3.

Results

Total 8 patients (6 NHL and 2 MM, median age: 55 years) who have failed in previous mobilization with conventional chemotherapy and G-CSF were tried again with high dose methotrexate, cytarabine and G-CSF. (table 1) Successful collection of CD34+ cells (> 5 × 106/kg) was achieved in six patients (75%). The total yield of CD34+ cells per kg of body weight harvested by 3 to 5 apheresis procedures was 6.28 × 106/kg (median; range, 1.53– 10.09 × 106/kg). (table 2)

Conclusion

High dose-MTX and cytarabine plus G-CSF may be a feasible chemotherapeutic regimen for stem cell mobilization in NHL and MM patients who have failed in previous mobilization with other type of chemotherapy and G-CSF.

Table 1.

Patients characteristics and mobilization outcome (1st & 2nd °°mobilization)

NAgeDiagnosisPrevious Treatmentprevious Mobilization regimen(1st)No. Of apheresis in 1st mobilizationTotal CD34+ yield (x106/kg ) in 1st mobilizationNo. Of apheresis in 2nd mobilizationTotal CD34+ yield (x106/kg ) in 2nd mobilizationCumulative CD34+ yield (x106/kg ) in 1st & 2nd mobilization
1 48 PTCL CHOP SMILE SMILE 4 4.03 3 3.7 7.73 
2 57 MZL RCVP ESHAP ESHAP 4 1.88 4 5.33 7.21 
3 59 MCL CHOP ESHAP ESHAPHD Ara-C 3,4 0.67, 1.53 3 1.53 3.73 
4 54 MM VAD PAD CYC 4 4.73 4 10.09 14.82 
5 64 PTCL CHOP ESHAP ESHAP 2 0.6 4 7.01 7.61 
6 45 DLBCL RCHOP ESHAP ESHAP 3 1.12 5 7.73 8.85 
7 62 MM VAD PAD CYC 4 3.76 3 9.21 12.97 
8 42 EN NK/T cell lymphoma VIPD CYC 5 3.16 4 5.55 8.71 
NAgeDiagnosisPrevious Treatmentprevious Mobilization regimen(1st)No. Of apheresis in 1st mobilizationTotal CD34+ yield (x106/kg ) in 1st mobilizationNo. Of apheresis in 2nd mobilizationTotal CD34+ yield (x106/kg ) in 2nd mobilizationCumulative CD34+ yield (x106/kg ) in 1st & 2nd mobilization
1 48 PTCL CHOP SMILE SMILE 4 4.03 3 3.7 7.73 
2 57 MZL RCVP ESHAP ESHAP 4 1.88 4 5.33 7.21 
3 59 MCL CHOP ESHAP ESHAPHD Ara-C 3,4 0.67, 1.53 3 1.53 3.73 
4 54 MM VAD PAD CYC 4 4.73 4 10.09 14.82 
5 64 PTCL CHOP ESHAP ESHAP 2 0.6 4 7.01 7.61 
6 45 DLBCL RCHOP ESHAP ESHAP 3 1.12 5 7.73 8.85 
7 62 MM VAD PAD CYC 4 3.76 3 9.21 12.97 
8 42 EN NK/T cell lymphoma VIPD CYC 5 3.16 4 5.55 8.71 

Abbreviations: PTCL=Peripheral T-cell Lymphoma; MZL=Marginal Zone Lymphoma; MCL=Mantle Cell Lymphoma; MM=Multiple Myeloma; EN=extra nodal; DLBCL=Diffuse Large B-cell Lymphoma; CHOP=cyclophosphamide, doxorubicin, vincristine, prednisolone; SMILE=dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide; RCVP=rituximab, cyclophosphamide, vincristine, prednisolone; ESHAP=etoposide, methylprednisolone, cytarabine, cisplatin; VAD=vincristine, doxorubicin, dexamethasone; PAD=bortezomib, doxorubicin, dexamethasone; RCHOP=rituximab+CHOP; VIPD=etoposide, ifosfamide, cisplatin, dexamethasone; HD Ara-C=high dose cytarabine; CYC=cyclophosphamide; No.=number;

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Table 2.

Remobilization of CD34+ cells after HD-MTX and cytarabine plus G-CSF

NApheresis 1Apheresis 2Apheresis 3Apheresis 4Apheresis 5Cumulative CD34+ yield (x106/kg)
1 0.12 1.54 2.04   3.7 
2 0.67 1.89 0.89 1.88  5.33 
3 0.29 0.76 0.48   1.53 
4 1.83 1.29 3.69 3.18  10.09 
5 0.41 0.95 3.26 2.39  7.01 
6 0.39 0.47 1.87 1.54 3.46 7.73 
7 1.35 3.09 4.77   9.21 
8 1.12 1.27 2.02 1.14  5.55 
Median (range) 0.54 (0.12−0.83) 1.28 (0.47−3.09) 2.03 (0.48−4.77) 1.88 (1.14−3.18) 3.46 (3.46) 6.28 (1.53 – 10.09) 
NApheresis 1Apheresis 2Apheresis 3Apheresis 4Apheresis 5Cumulative CD34+ yield (x106/kg)
1 0.12 1.54 2.04   3.7 
2 0.67 1.89 0.89 1.88  5.33 
3 0.29 0.76 0.48   1.53 
4 1.83 1.29 3.69 3.18  10.09 
5 0.41 0.95 3.26 2.39  7.01 
6 0.39 0.47 1.87 1.54 3.46 7.73 
7 1.35 3.09 4.77   9.21 
8 1.12 1.27 2.02 1.14  5.55 
Median (range) 0.54 (0.12−0.83) 1.28 (0.47−3.09) 2.03 (0.48−4.77) 1.88 (1.14−3.18) 3.46 (3.46) 6.28 (1.53 – 10.09) 
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Disclosures:

No relevant conflicts of interest to declare.

Topics:
chemotherapy regimen, cytarabine, cytokine, lymphoma, non-hodgkin, methotrexate, multiple myeloma, apheresis, granulocyte colony-stimulating factor, recombinant granulocyte colony stimulating factor, lymphoma

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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