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07-31-2010, 12:37 PM
Double Stem Cell Transplant With Low-Dose And High-Dose Melphalan Is An Effective Treatment For Multiple Myeloma

By Michelle Spektor, "The Myeloma Beacon"
Jul 30, 2010

The results of a recent study suggest that consecutive low-dose melphalan and high-dose melphalan treatment combined with autologous stem cell transplants is an effective treatment for multiple myeloma patients with manageable side effects.
?The low-dose melphalan step led to complete response and very good partial response rates similar to those of combinations containing Velcade and steroids at a fraction of the cost,? wrote Dr. Nicolas Novitzky, the study?s lead author, in an email to The Myeloma Beacon.
Melphalan (Alkeran) is a chemotherapeutic drug that is frequently used in combination with stem cell transplants to treat younger multiple myeloma patients. Melphalan can cause severe side effects, including neutropenia (low white blood cell count), nausea, and blood-related complications. Higher doses of melphalan are usually associated with more severe side effects.
A previous study showed, however, that higher doses of melphalan are more effective than lower doses in myeloma treatment and preparation for stem cell transplants (see related Beacon news).
Dosage and optimal sequencing of melphalan treatment therefore continue to be investigated.
In their study, the researchers from South Africa investigated the use of low-dose melphalan plus stem cell transplant followed by high-dose melphalan plus stem cell transplant as a potential treatment strategy for multiple myeloma.
The researchers recruited 42 multiple myeloma patients, all of whom were in stage 2 or 3 progression of the disease. Median age of the study participants was 53 years.
The patients first received dexamethasone (Decadron) induction treatment for four 28-day cycles. Stem cells were collected from each participant and stored for future supplementation. Each participant then received a 100 mg/m2 infusion of melphalan, followed by a stem cell transplant the next day.
Six months later, the participants received 100 mg/m2 infusion of melphalan on two consecutive days, for a total dosage of 200 mg/m2, followed by a second stem cell transplant.
Patients were evaluated four times during the trial: after induction therapy with dexamethasone, after the first transplant, after the second transplant, and at a median follow-up of 6 days.
Twenty-five patients (61 percent) responded to the induction treatment with dexamethasone. Two patients were in complete remission, three exhibited a very good partial response, and 20 exhibited a partial response.
After the first stem cell transplant, the number of participants in complete remission increased to seven and the number of participants who achieved a very good partial response increased to nine.
After the second stem cell transplant, 20 patients (48 percent) were in complete remission, 14 patients (33 percent) exhibited a very good partial response, and six patients (14 percent) exhibited a partial response.
At a median follow-up of 648 days, eight patients had died. One death was related to treatment procedures, six were due to disease progression, and one was due to an unrelated accident. Median survival had not been reached yet.
All patients experienced severe side effects at different points throughout the study.
Blood-related side effects that resulted from the 100 mg/m2 transfusion of melphalan required 16 participants to receive blood transfusions. In addition, 15 participants were admitted to the hospital due to high fever from neutropenia (low white blood cell count), nausea, and mucositis (inflammation of the lining of the digestive tract).
The 200 mg/m2 infusion of melphalan elicited similar side effects among all participants, but with more gastrointestinal complications.
?Toxicities were different and related to marrow suppression, which was universal,? explained Dr. Novitzky. ?But with close follow up and prophylactic antibiotics, they were acceptable.?
The researchers concluded that despite the side effects, the evaluated treatment strategy resulted in positive long-term outcomes for the patients.
For more information, please refer to the study in the journal of the American Society for Blood and Marrow Transplantation (abstract).