ORLANDO--A preparative regimen employing a radiolabeled monoclonal antibody
(MoAb), coupled with busulfan (Myleran) and cyclophosphamide (Cytoxan,
Neosar), yielded a low relapse rate in patients with acute myelogenous
leukemia (AML) undergoing bone marrow transplantation (BMT) while in first
"Although follow-up is short," Dana C. Matthews, MD, said
in her presentation at the ASH meeting, "we are very encouraged by
the low relapse rate."
Despite advances over the last two decades, AML patients undergoing
BMT during first remission have shown no appreciable improvements in disease-free
survival, said Dr. Matthews, of the Fred Hutchinson Cancer Research Center.
Increasing the radiation dose used in the preparative regimen lowers
the relapse rate in these patients, according to previous studies conducted
at Hutchin-son, but has no impact on overall disease-free survival, she
said. Moreover, the higher radiation doses produce greater toxicity to
normal organs, eg, the liver.
In contrast, use of an anti-CD45 murine MoAb labeled with iodine-131
enabled Dr. Matthews and her colleagues to safely deliver almost 11 Gy
of radiation to marrow in 17 AML patients, ranging in age from 16 to 55
years, who were to receive a marrow graft from an HLA-matched, related
In this phase I/II study, patients first received a trace dose of the
radiolabeled MoAb followed by gamma camera imaging and a bone marrow biopsy
to determine the estimated dose to target organs (spleen, bone marrow)
and nontarget organs (liver, lung, kidney). These individualized radiation
absorbed doses were used to calculate desired therapeutic doses of the
MoAb, Dr. Matthews said.
The therapeutic doses were administered over 4 to 8 hours on the 14th
day before transplantation and were followed by treatment with busulfan
(16 mg/kg/day) on the eighth through fifth days prior to grafting and cyclophosphamide
(120 mg/kg/day) on the third and second days preceding BMT.
She noted that no grade 3 or 4 regimen-related toxicity occurred in
the first four patients, who received a lower radiation dose (105 to 152
mCi of iodine-131, which delivered an average of 3.5 Gy to the liver and
9.2 Gy to the marrow).
Use of a higher level of radiation (101 to 263 mCi of iodine-131, delivering
an average of 5.25 Gy to the liver and 10 Gy to the marrow) in the next
13 patients resulted in three cases of grade 3 toxicity (mucositis) and
one instance of grade 4 toxicity. The patient with grade 4 toxicity died
of multiorgan failure, she added.
In the surviving 16 patients, no relapses have occurred over a median
follow-up of 14 months. One patient is still alive 33 months after transplant.
Although continued accrual and longer follow-up are needed to ascertain
true toxicity rates and the durability of remissions, Dr. Matthews believes
that the new therapy "should improve disease-free survival in AML
patients in first remission."