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Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
January 1989,
Lijecnicki vjesnik,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
February 1992,
Gan to kagaku ryoho. Cancer & chemotherapy,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
January 1987,
Cancer treatment reports,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
January 1989,
Cancer chemotherapy and pharmacology,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
August 1993,
Bone marrow transplantation,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
November 1985,
Revue francaise de transfusion et immuno-hematologie,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
January 1979,
Experimental hematology,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
April 1986,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
October 1993,
Bone marrow transplantation,
H M Lazarus, and
R H Herzig, and
J Graham-Pole, and
S N Wolff, and
G L Phillips, and
S Strandjord, and
D Hurd, and
W Forman, and
E M Gordon, and
P Coccia
April 1989,
European journal of cancer & clinical oncology,
