Continuous Infusion Cyclophosphamide and Low Dose Total Body Irradiation (CICy/ldTBI) As a Conditioning Regimen for Tandem Autologous Transplant in Multiple Myeloma

Cytotoxic therapy and autologous stem cell transplant (ASCT) remain the mainstay of multiple myeloma (MM) treatment due to both depth of remission as well as relative safety. Improvements in event free survival (EFS) and overall survival (OS) have been reported in patients undergoing tandem transplant. High-dose melphalan (200mg/m²) is one of the most widely used conditioning regimens. Its use, however, is associated with high levels of toxicity with transplant related mortality (TRM) approaching 5% in some studies. When total body irradiation (TBI) is added to melphalan, the risk of infectious complications and TRM increase.

Between June 2001 and July 2011, 21 MM patients underwent tandem ASCT at our institution as part of a prospective phase II clinical study. The patients received cyclophosphamide (CY), busulphan, and etoposide as a conditioning prior to their first ASCT. Patients were assessed after the first ASCT and offered either 2^nd tandem ASCT if they achieved ≤ partial remission (PR) or maintenance therapy if they achieve ≥ very good partial remission (VGPR). For patients undergoing tandem ASCT, a novel conditioning regimen was used which included: cyclophosphamide 1500mg/m²/day continuous IV infusion on day -7 through day -4 followed by twice daily TBI at 150 cGy on day -2 and -1. Melphalan 140 mg/m²was substituted for TBI if prior radiation did not allow for further irradiation.

The median patient age was 59 years (51–70) and the group consisted of 10 males and 11 females. 17 patients received CICy/ldTBI while 4 patients received CY/melphalan due to prior history of radiation. At the time of the 2^ndASCT, 18 patients were in PR, 2 were in VGPR, and 1 had progressive disease (PD). Information regarding the duration of neutropenia, presence of neutropenic fever, infectious complications, and transfusion requirements were collected. Treatment response assessment was based on the uniform response criteria published by The International Myeloma Working Group.

Median duration of neutropenia with CICy/ldTBI was 10 days (range, 8–20). 16 patients (76.2%) developed at least one neutropenic fever episode of >38° C. After fever, mild diarrhea was the most common adverse effect (42.9%). 1 patient each (4.8%) developed a limited subdural bleed, pulmonary embolus, neutropenic colitis, bacterial pneumonia, possible fungal pneumonia, hemorrhagic cystitis, and septic shock. 19 patients (90.5%) required transfusion support (red blood cells, platelets, or both) in the post-transplant period. Grade I-II mucositis was seen in 4 patients. All patients were alive at D100. After tandem transplant, 4 patients had entered complete remission (CR) (19.0%). There were 7 VGPR (33.3%) and 6 patients were in PR (28.6%). The median progression free survival (PFS) and overall survival (OS) was 20 and 38 months, respectively.

Our results suggest favorable outcomes without TRM in a selected group of high risk myeloma patients who receive CICy/ldTBI as a conditioning regimen prior to their second tandem ASCT.

No relevant conflicts of interest to declare.