Multiple-drug chemotherapy for acute leukemia.The TRAMPCOL regimen: Results in 86 patients

Abstract

A combination of eight cytotoxic drugs, administered simultaneously, has been used in 86 cases of acute leukemia. The regimen, designated TRAMPCOL, incorporated thioguanine, rubidomycin, (daunorubicin), ytosine arabinoside, methotrexate, prednisolone, cyclophosphamide, vincristine, and usually L-asparaginase. Treatment was administered in five-day pulses with treatment-free intervals varying from nine to 23 days. Subjective and objective toxic effects were not more severe than those seen with two-and four-drug regimens previously employed. Substantial clinical and hematologic improvement occurred in 8/19 patients with chronic granulocytic leukemia (CGL) in acute transformation. Complete clinical and hematologic remission (CR) was achieved in 3/7 patients with untreated acute myeloid leukemia (AML), 5/19 patients with AML who had failed to achieve CR with other therapy, and 4/18 patients with AML in relapse after CR obtained with regimens other than TRAMPCOL. CR occurred in 15/17 patients with acute lymphocytic leukemia (ALL), most of whom had had multiple previous relapses. CR was not achieved in four patients with AML superimposed on pre-existing myeloproliferative disorders. The TRAMPCOL regimen merits further evaluation in CGL after acute transformation, as a primary treatment for AML, and as therapy for ALL 1) in relapse, 2) in adults, 3) in children with adverse prognostic features, and 4) in T-cell ALL. Cancer 4O:ZO-29, 1977. N 197 1 ONE OF US DEVISED A NEW DRUG RECI-I men for trial in patients with chronic gran-ulocytic leukemia (CGL) which had undergone acute transformation. l9 In choosing this regi-men, the factors taken into account were 1) the poor results of other treatments;'*8* 10,11,2e 2) the presence, in many cases, of multiple clones of leukemic cells, which might have diverse sensitivities to drugs;21-zs and 3) the clinical observation that responses to single agents, as measured by reduction of leukocytosis, though sometimes marked, were generally transient, and drug resistance appeared to arise very rapidly. These considerations suggested that a multiple-agent chemotherapy was desirable. The results of a four-drug regimen had been poor,8 and it was

Haematology at the Hammersmith Hospital and Royal Postgraduate Medical School 1934–1994

“…A military man by inclination, he produced ‘heavy artillery’ regimens, aiming to gain efficacy without increasing toxicity by combining drugs with different modes of action and toxicities (e.g. Spiers et al , 1974, 1977). He was also, with John Goldman, one of the first at HH to perform research on CML (Spiers et al , 1975).…”

Allogeneic bone marrow transplantation vs chemotherapy for the treatment of childhood acute lymphoblastic leukaemia in second complete remission (revisited 10 years on)

“…Seven patients refused further intensive CT treatments and also died. The remaining 25 were treated with standard four drug induction or salvage CT protocols, mainly the TRAMPCOL regimen, 13 with discouraging results since only four patients attained a very short third CR and all eventually died of pancytopenia, disease progression and one patient at day +1690 of multifocal leukoencephalopathy. Median interval from relapse to death was 0.46 years (range 0.02-1.05 years).…”

Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase

“…New agents, combination regimens, and stem cell transplantation strategies (preparative regimens, graft versus host disease prophylaxis, antibiotic prophylaxis, source of stem cells) continue to be explored to improve prognosis in CML‐BP. Recent promising new agents include decitabine, cladribine, troxacitabine, tiazofurin, and most importantly the new signal transduction inhibitor 571 (STI571; imatinib mesylate), a Bcr‐Abl tyrosine kinase inhibitor, recently renamed Gleevec 6–18…”