The Efficacy of Plerixafor Plus Recombinant Human Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Lymphoma and Plasma Cell Diseases

Objective: Plerixafor is a small-molecule inhibitor of CXCR4. This study evaluates the efficacy of plerixafor combined with recombinant human granulocytic colony stimulating factor(G-CSF), in mobilizing hematopoietic stem cells for autologous stem-cell transplantation (ASCT) in patients with lymphoma and plasma cell diseases.

Methods: A retrospective analysis was performed on 41 patients with Plerixafor combined with G-CSF admitted to the Department of Hematology, Nanfang Hospital, Southern Medical University,China from July 2019 to February 2021. Mobilization protocol: all patients were given G-CSF 10μg/kg d1-4 and Plerixafor 20mg (all patients weighed less than 83kg) 11 hours before collection on day 5 (night of day 4).

Results: The median age of 41 patients was 52 years (25-66 years), the median body weight was 57kg (41-80kg), and the male to female ratio was 1.16:1(22/19). The patients of plerixafor used in combination with G-CSF include Multiple Myeloma 75.6%(31/41), Diffuse Large B Cell Lymphoma was 9.8%(4/41), Peripheral T Cell Lymphoma (4.9%, 2/41), Angioimmunoblastic T Cell Lymphoma (2.4% ,1/41), Systemic light chain (AL) amyloidosis (2.4% ,1/41), POEMS syndrome (2.4%,1/41), and plasma cell leukemia (2.4%, 1/41). Above the patients got partial remission（PR） before mobilization. 17 patients got complete remission（CR）, 4 patients got very good PR(VGPR) and ten got PR. There were 5 lymphoma patients with CR and 2 with PR. The majority of patients, 25, received first-line chemotherapy. 11 patients received second-line chemotherapy, and five received third-line myeloma therapy or above. The median cycle of chemotherapy was 4 (range 4-41). Twenty-two patients with multiple myeloma received treatment with lenalidomide regimens. 26 of all (63.4%) had optimum mobilization (CD34 positive cell count ≥5 × 10 ⁶ cells/kg), and 36 (87.8%) had minimum mobilization (CD34 positive cell count ≥2 × 10 ⁶ cells/kg). The minimum and optimum mobilization rate of first-line chemotherapy regimen was 92% and 72% respectively. The rate of the minimum mobilization of the second line chemotherapy was 100%, the optimum mobilization rate was 63.6%. The minimum and the optimum mobilization rate were 60% and 20% for the third line chemotherapy and above. The minimum mobilization rate was 94.7% and the optimum mobilization rate was 57.9% in patients receiving lenalidomide containing chemotherapy less than the 4 cycles. The minimum and optimum mobilization rate were 66.7% and 66.7% for patients with more than 4 cycles of lenalidomide chemotherapy. Thirty-four patients received autologous hematopoietic stem cell transplantation. Conditioning regimens was TBI (total-body irradiation) + CY (CTX)+ VP-16 or BUCY+ Me-CCNU protocol in lymphoma patients, and Melphala 200mg/m ² in Multiple myeloma patients. A reduction of melphalan dose(140mg/m ²) in patients with severe renal failure, here defined as iohexol clerarance <30 ml/min, is suggested. Neutrophil engraftment was defined as neutrophil count ≥ 0.5 × 10 ⁹/L for 3 days or ≥ 1.0 × 10 ⁹/L for 1 day. Platelet engraftment was defined as platelet count ≥ 20 × 10 ⁹/L without a transfusion from the preceding 7 days. All patients who received transplantation had successful neutrophil engraftment and 94.1% had successful platelet engraftment. The median time to engraftment was 10 days(9-13 days) for neutrophil and 11 days (9-48 days) for platelet. Using all available laboratory measurements and clinical information to determine graft failures, there were two platelet graft failures in at 1 month follow-up visit. However they had successful platelet engraftment after treatment with Eltrombopag or Avatrombopag(43 days, 48 days).

Conclusions: The mobilized cells after G-CSF plus Plerixafor contained high numbers of hematopoietic stem cells, and engrafted very efficiently. G-CSF plus Plerixafor may be preferred for ASCT in patients with lymphoma and plasma cell diseases.