Active Immunotherapy Used Alone for Maintenance of Patients with Acute Myeloid Leukaemia

Summary.-One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only. The present communication describes our experience over a 6-year period of 3 trials of active immunotherapy in AML in which immunotherapy has been associated with relatively short first remissions but easy second and subsequent remission with long post-relapse survival and an excellent quality of life. PATIENTS AND METHODSPatients entered into 3 Manchester AML trials since 1971 and followed up to 15 March 1977, have received one of the therapeutic protocols summarized in Table I. Patients were not selected, and all who were referred to Manchester Royal Infirmary were treated.The diagnosis of AML was confirmed by blood examination and by marrow examination carried out by sternal or iliac-crest puncture. The aspirated material was fixed,

contrasting

confidence: 57%

“…A blast count > 8 0 was taken as definite indication of relapse, even in the absence of clinical and peripheral blood changes. Immunotherapy with irradiated allogeneic AML blast cells and BCG (Glaxo) was administered at weekly intervals as described previously (Freeman et al, 1973).…”

mentioning

confidence: 99%

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions

Harris¹,

Zuhrie²,

Freeman³

et al. 1978

“…WE ARE treating a number of acute myeloid leukaemia (AML) patients during remission with active immunotherapy (see Freeman et al, 1973) and without maintenance chemotherapy. The treatment protocol is based on immunotherapy trials carried out at the Royal Marsden and St Bartholomew's Hospitals (Powles et al, 1973) and entails the weekly injection of x-irradiated allogeneic (donor) AML blasts subcutaneously into 3 of the patient's limbs and BCG into the fourth.…”

mentioning

confidence: 99%

Cell-mediated cytotoxicity as a result of immunotherapy in patients with acute myeloid leukaemia

Taylor¹,

Harris²,

Freeman³

1976

Summary.-Leucocytes from normal individuals and from patients with acute myeloid leukaemia (AML) in remission receiving active immunotherapy with allogeneic AML blasts (AML-I) were cultured for 6 days with AML-I blasts, Burkitt's lymphoma cells (BL) or lymphoblastoid cells (LCL). The leucocytes were then tested for cell-mediated cytotoxicity (CMC) against 51Cr-labelled AML-I, BL or LCL target cells. There was no substantial difference in the CMC of leucocytes from patients and normals cultured without stimulation, and tested against AML-I, BL or LCL targets. Patients' leucocytes stimulated in vitro with AML-I had a greater frequency of positive CMC responses against AML-I, BL and LCL than normal individuals. The results suggest that co-cultivation of leucocytes with AML-I blasts reactivates memory cytotoxic leucocytes in AML patients receiving immunotherapy and that this test may be useful in measuring the effectiveness of immunotherapy.

“…A group in Manchester (Freeman et al, 1973) followed the same immunotherapy protocol as used here, and, whilst they did not carry controls in their clinical trial, they commented on the ease with which patients who had received immunotherapy without maintenance chemotherapy achieved a second remission, and also noted the long period of survival after relapse in this group.…”

Section: Mechani8ms Of Prolongation Of Life By Immunotherapymentioning

confidence: 99%

Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient

Powles¹,

Russell²,

Lister³

et al. 1977

Summary.-One hundred and thirty-nine untreated patients with acute myelogenous leukaemia (AML) were admitted between August 1970 and December 1973 and allocated into two remission treatment regimens: one to receive chemotherapy alone and the other chemotherapy with immunotherapy. Of the patients who attained remission, 22 were in the chemotherapy group and in September 1975 2 remained alive, the median survival time being 270 days and after relapse 75 days. Twenty-eight patients received immunotherapy during remission, and 5 remained alive; the median survival time of the group being 510 days and after relapse 165 days. Ongoing actuarial analysis precisely predicted early in the study the median survival of the two groups, but it took a 2-year follow-up after entry of the last patient before it became clear that there were very few long-term survivors. The increase in survival time produced by the immunotherapy is apparently made up of two components: prolongation of the first remission and length of survival after the first relapse. It must be noted that the chemotherapy for this study was devised 6 years ago and the results of the control arm (chemotherapy alone) may be poorer than those obtained in contemporary studies.