Whole blood harvested after granulocyte-colony stimulating factor (Neupogen) mobilization, and reinfused unprocessed after high-dose melphalan treatment, accelerates hematopoietic recovery in patients with multiple myeloma

V Raina, A Sharma, R Kumar, M Bhargava
Cancer 1996 March 15, 77 (6): 1073-8

BACKGROUND: High-dose melphalan (HDM) is now a standard treatment for multiple myeloma (MM). Stem cell transplants are fast evolving as an alternative to bone marrow transplants because they are less traumatic and easier to perform. A study was undertaken to test if whole blood harvested after mobilizing peripheral blood stem cells with granulocyte-colony stimulating factor (G-CSF) reinfused as such (without stem cells being processed or concentrated through a cell separator) for rescue after HDM (dose 140-180 mg/m2) in MM accelerates hematopoietic recovery.

METHODS: Eight consecutive patients with MM were given HDM after receiving 4-5 courses of infusional vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. Approximately 6 weeks after the last course of chemotherapy, at the start of the procedure, G-CSF (Neupogen) was given at a dose of 10 microgram/kg subcutaneously daily for 4 days to mobilize stem cells. All of the patients had brisk leukocytosis (18.4-64.6 x 10(9)/L). On day 0 (fifth day after G-CSF), 1 L of blood was removed by phlebotomy and kept at room temperature for 24 hours. This was followed by a rapid intravenous (i.v.) bolus of melphalan at a dose of 140 mg/m2 in the first three patients, 155 mg/m2 in the 4th, 170 mg/m2 in the 5th, and 180 mg/m2 in the 6th, 7th, and 8th patients, applies to all patients along with hydration and diuresis. Twenty-four hours later, I L of blood previously removed was transfused back to the patient without any processing through the cell separator. The numbers of mononuclear cells reinfused was between 0.76 and 3.2 x 10(8)/kg (mean: 1.82 x 10(8)/kg). The number of CD 34+ cells infused in 4 patients ranged from 1.9 to 2.8 x 10(6)/kg (mean: 2.35 x 10(6)/kg). G-CSF was restarted on day 2 at a dose of 5 microgram/kg and given daily until the granulocyte count was 0.5 x 10(9)/L or more for 3 consecutive days. Antibiotics were given whenever a patient developed pyrexia. Platelets were transfused if below 20 x 10(9)/L or for incidences of overt bleeding.

RESULTS: Granulocyte counts touched 0 between Days 6 and 10, lasting for an average of 3.4 days. Duration of granulocyte count below 0.5 x 10(9)/L was 6.5 days (range: 5-9), and these rose to 1.0 or more x 10(9)/L by Day 13.7 (range: 13-16). The number of platelet transfusions given per patient was 2.5 (range: 0-4). Intravenous antibiotics were used for 9 days (range: 4-12), and patients were discharged on Day 19 (range: 16-22). Follow-up ranged from 45 to 380 days.

CONCLUSIONS: Hematopoietic recovery was rapid in all patients, including those who received doses of melphalan higher than 140 mg/m2. This resulted in less need for platelet transfusions or antibiotics, and hospitalization was short. Our results are historically similar to conventional peripheral blood stem cell transplants but much better than autologous bone marrow transplants, indicating that whole blood after G-CSF provided sufficient progenitor cels for early engraftment. The procedure is less labor intensive insofar as it does not require separation and concentration of stem cells. It has the potential of becoming an alternative to autologous marrow and peripheral blood stem cell transplantation in patients with MM.

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