Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia

Summary. The MRC UKALL IX trial for patients with untreated ALL aged 14 years and over was open to new patients from July 1980 to April 1985. 266 patients were randomized between two induction schedules, M (involving intermediate dose rnethotrexate with folinic acid rescue) and D (involving daunorubicin). Schedule M resembled that used in the previous MRC adult ALL, trial (UKALL VI). while schedule D was somewhat more intensive. No difference in disease-free survival was found between the treatment arms, but patients on the daunorubicin arm went into remission earlier.
The overall remission rate was 8 7%, which is at least as good as in contemporary studies elsewhere: factors predictive of a lower remission rate were older age and higher WBC. For those who entered remission, WBC, age and sex were the most important prognostic factors. Time to achieve remission was not a significant factor after allowance was made for these.
An historical comparison does not show any improvement over the preceding MRC adult trial, although the subsequent trial does show a modest improvement at present. Because the improved outlook seen in children is not apparent in adults, and no other randomized trial has demonstrated substantial benefit for any particular regimen, the next trial, UKALL XII, will be investigating the benefit or otherwise of bone marrow transplantation.     

Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI)

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles.     

Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension. Medical Research Council Working Party on Mild Hypertension.

Seventeen thousand three hundred and fifty four mildly hypertensive people with diastolic blood pressures between 90 and 109 mm Hg at screening were randomised to active treatment, with bendrofluazide or propranolol, or to placebo tablets. They were followed for a maximum of five and a half years, giving a total of 85,572 patient-years of observation. There were 456 myocardial infarctions or sudden coronary deaths. Drug treatment did not affect the overall rate of coronary events. Rates per thousand person-years were 8.3 and 9.0 in men and 1.8 and 1.7 in women in the active treatment and placebo groups respectively. Event rates were much higher in smokers than in non-smokers on placebo treatment (12.6 and 7.5 in men and 3.5 and 1.0 in women in smokers and non-smokers respectively). An analysis of subgroup results showed a lower event rate in non-smoking men on propranolol than in non-smokers on placebo (5.0 and 7.5 per thousand person-years respectively). Bendrofluazide had no apparent effect on the event rate. The interaction between the type of treatment (propranolol, bendrofluazide, or placebo) and smoking in determining the coronary event rate was not statistically significant, however. The incidence of electrocardiographic changes of silent infarction--that is major Q/QS abnormalities--differed little with sex, smoking habit, or treatment with either active drug.     

The Relation between Morphology and Other Features of Acute Myeloid Leukaemia, and their Prognostic Significance: Report of the Medical Research Council's Working Party on Leukaemia in Adults

272 cases of acute myeloid leukaemia at all ages were allocated on the basis of May-Grünwald-Giemsa stained films of peripheral blood and bone marrow to seven morphological categories (M0-M6), four of which were sub-divided into poorly-differentiated and well-differentiated types. In all, 131 cases were considered to be poorly differentiated and 141 cases well differentiated. The 19 cases diagnosed as hypergranular promyelocytic leukaemia (M₃) formed a distinct and homogeneous group in respect of their low mean age, high incidence of haemorrhagic phenomena at presentation, low mean platelet count and neutrophil count, low remission rate and short survival. Aside from this group no significant relationships were apparent between the other morphological categories and the occurrence of remission and the duration of survival, although the duration of survival was slightly though not significantly shorter in the poorly-differentiated group.     

Treatment-related deaths during induction and first remission of acute myeloid leukaemia in children treated on the Tenth Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10)

Between 1988 and 1995, 341 children with acute myeloid leukaemia (AML) were treated on the Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10). The 5-year overall survival was 57%, much improved on previous trials. However, there were 47 deaths (13. 8%), 11 of which were associated with bone marrow transplantation (BMT). The treatment-related mortality was significant at 13.8%, but decreased in the latter half of the trial from 17.8% in 1998-91 to 9. 6% in 1992-95 (P = 0.03%). The main causes of death were infection (65.9%), haemorrhage (19.1%) and cardiac failure (19.1%). Fungal infection was a significant problem, causing 23% of all infective deaths. Haemorrhage occurred early in treatment, in children with initial white cell counts >100 x 109/l (P = 0.001), and was more common in those with M4 and M5 morphology. Cardiac failure only occurred from the third course of chemotherapy onwards, with 78% (7/9) in conjunction with sepsis as a terminal event. Some deaths could be prevented by identifying those most at risk, and with prompt recognition and aggressive management of complications of treatment. Future options include the prophylactic use of antifungal agents, and the use of cardioprotectants or alternatives to conventional anthracyclines to decrease cardiac toxicity.     

Failure of a new protocol to improve treatment results in paediatric lymphoblastic leukaemia: lessons from the UK Medical Research Council trials UKALL X and UKALL XI

The impact of various types of intensification therapy was examined in a cohort of 3617 children aged 1-14 years with acute lymphoblastic leukaemia (ALL) enrolled in the Medical Research Council (MRC) UKALL X (1985-90) and UKALL XI (1990-97) trials. UKALL XI was modified in 1992 to incorporate the "best arm" of UKALL X with two 5-d intensification blocks at 5 and 20 weeks, and an additional randomization in respect of a third intensification at 35 weeks but omission of two consecutive injections of daunorubicin during induction. All children were eligible for randomization irrespective of risk group. The impact of the various types of intensification therapy was examined in a stratified analysis. At a median follow up of 102 months, both trials had an identical event-free survival of 61% (95% CI 58-63%) at 8 years. Survival at 8 years in UKALL XI was significantly better in than in UKALL X, 81% (79-83%) compared with 74% (72-76%) (P = < 0.001), owing to improved management of relapse. There was a highly significant trend in reduction of the number of relapses and deaths with increased intensity of therapy both for children with initial leucocyte count < 50 x 10(9)/l (P = < 0.001) and > or = 50 x 10(9)/l (P = 0.002). Introduction of a third late intensification block compensated for omission of anthracyclines during induction but produced little additional benefit. These results show, in a large cohort of patients, that minor modifications of therapy may influence relapse rate and obviate the benefit of previous randomized trials. The failure to adapt treatment for higher risk children contributed to these disappointing results.     

Allogeneic stem cell transplantation of adult chronic myelomonocytic leukaemia. A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

We report the results of 50 allogeneic transplantations from related (n = 43) or unrelated (n = 7) donors, performed for chronic myelomonocytic leukaemia (CMML) in 43 European centres. The median age at transplant was 44 years (range 19-61). Eighteen patients had excess blasts ranging from 5% to 30% at the time of transplantation. Two graft failures were observed (4%). Neutrophil (> 0.5 x 109/l) and platelet engraftment (> 50 x 109/l) was reached after a median of 17 d (range 11-38) and 27 d (range 11-48) respectively. Acute graft-versus-host disease (GvHD grade II-IV was seen in 35% of patients, while 20% developed severe-acute GvHD grade III/IV. Twenty-six patients (52%) died of treatment-related causes. After a median follow-up of 40 months (range 11-110), the 5-year-estimated overall survival was 21% (95% CI: 15-27%) and the 5-year-estimated disease-free survival (DFS) was 18% (95% CI: 13-23%). Earlier transplantation in the course of disease, male donor, use of unmanipulated grafts, allogeneic transplantation and occurrence of acute GvHD favoured better DFS, but did not reach statistical significance. The 5-year estimated probability of relapse was 49%. The data showed a trend for a lower relapse probability of acute GvHD grade II-IV (24% vs 54%; P = 0.07), and for a higher relapse rate in patients with T cell-depleted grafts (62% vs 45%), suggesting a 'graft-versus-CMML effect'.     

Randomized placebo-controlled trial of granulocyte colony stimulating factor (G-CSF) as supportive care after induction chemotherapy in adult patients with acute myeloid leukaemia: a study of the United Kingdom Medical Research Council Adult Leukaemia Working Party

The role of granulocyte colony stimulating factor (G-CSF) as supportive therapy following intensive induction chemotherapy for acute myeloid leukaemia (AML) in adults was investigated in a randomized trial. G-CSF (Lenograstim, 263 μg/d) or placebo was administered from day 8 after the end of chemotherapy until neutrophil recovery to 0·5 × 10⁹/l (or for up to 10 d). Eight hundred and three patients were entered. Neutrophil recovery was quicker with G-CSF ( P  < 0·0001), but this did not lead to differences in the number, severity or duration of infections. There were no substantial supportive care savings, although G-CSF patients spent 2 d less in hospital ( P  = 0·01). Complete remission (CR) rates were similar between arms (73% G-CSF, 75% placebo, P  = 0·5), as were reasons for failure (induction death: P  = 0·7; resistant disease: P  = 0·5) and, for remitters, 5-year disease-free survival (34% vs. 38%, P  = 0·3). Overall survival at 5 years was 29% with G-CSF vs. 36% with placebo ( P  = 0·10). Both CR rate ( P  = 0·006) and overall survival ( P  = 0·006) were worse with G-CSF in patients aged <40 years, but this may be a chance effect. There is some evidence from this trial of an adverse effect of G-CSF but these data need to be viewed in the context of the evidence from the other trials.     

Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML/RARalpha rearrangement in newly diagnosed AML. The Medical Research Council (MRC) Adult Leukaemia Working Party

Acute promyelocytic leukaemia (APL) is characterized by the t(15;17) leading to the formation of PML-RARalpha and RARalpha-PML fusion genes; this rearrangement has been considered both diagnostic for, and restricted to, this subtype of acute myeloid leukaemia (AML FAB M3). We describe two cases of AML with the t(15;17) associated with a PML/RARalpha rearrangement which lacked typical APL morphology, classified as FAB M1 and M2 respectively. In both cases morphological review revealed small populations of cells which exhibited some features associated with APL. In the case classified as M1, PML immunofluorescence studies revealed the classic microparticulate nuclear staining pattern as observed in typical cases of APL with the t(15;17). Similarly, blasts from this case were found to be sensitive to ATRA in vitro as determined by NBT reduction test and by normalization of the PML nuclear body staining pattern. To determine the frequency of PML/RARalpha rearrangements in FAB subtypes other than M3, 530 patients from the MRC AML trials were screened using nested RT-PCR. Only one individual, initially classified as M5 with a normal karyotype, was found to have a PML/RARalpha rearrangement. The diagnosis was revised to M3 variant on subsequent morphological review. In conclusion, this study demonstrates that, in rare cases, the t(15;17) is not restricted to patients with M3 morphology as defined by current FAB criteria. Therefore, although we consider cytogenetic analysis of newly diagnosed cases of AML to be mandatory, our data suggests that routine molecular screening for PML/RARalpha rearrangements is not justified and should be reserved for those cases displaying features which may be suspicious of APL even if such cells comprise only a minority of the total population.     

Haematopoietic stem cell transplantation for patients with myelo-dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Allogeneic stem cell transplantation from an HLA-identical sibling donor is a curative treatment option for a young patient with myelodysplastic syndrome, limited by age and lack of sibling donors. Alternative stem cell sources have been used more recently, such as unrelated donors, non-identical family members or autologous transplants. This analysis of 1378 transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) addresses the outcome of the varying procedures according to the known risk factors. The estimated disease-free survival (DFS) and estimated relapse risk at 3 years were both 36% for 885 patients transplanted with stem cells from matched siblings. In the multivariate analysis, age and stage of disease had independent prognostic significance for DFS, survival and treatment-related mortality. Patients transplanted at an early stage of disease had a significantly lower risk of relapse than patients transplanted at more advanced stages. The estimated DFS at 3 years was 25% for the 198 patients with voluntary unrelated donors, 28% for the 91 patients with alternative family donors and 33% for the 126 patients autografted in first complete remission. The non-relapse mortality was 58% for patients with unrelated donors, 66% for patients with non-identical family donors and 25% for autografted patients. The relapse rate of 18% was relatively low for patients with non-identical family donors, 41% for patients with unrelated donors and 55% for patients treated with autologous stem cell transplantation. Both allogeneic and autologous stem cell transplantation have emerged as treatment options for patients with myelodysplastic syndromes. Transplantation with an HLA-identical sibling donor is the preferred treatment option. Patients without an HLA-identical sibling donor may be treated with either autologous stem cell transplantation or an alternative donor transplantation. Patients younger than 20 years may be treated with an unrelated donor transplantation. Patients older than 40 years, and probably also patients between 20 and 40 years, may benefit most from an autologous stem cell transplantation.     

Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation

Although second allogeneic haematopoietic cell transplantation (allo-HCT2) is a therapeutic option for patients relapsing after first HCT (allo-HCT1), there is limited data on allo-HCT2 in patients with acute lymphoblastic leukaemia (ALL). We retrospectively studied 245 patients receiving allo-HCT2 as a salvage treatment for relapse following allo-HCT1 between the 2000 and 2017. The median age at allo-HCT2 was 34·6 years (range: 18–74). One hundred and one patients (41%) received sibling donor and 144 (59%) unrelated donor allo-HCT2. Acute graft-versus-host disease (GVHD) grade II–IV and III–IV occurred in 33% and 17% of the patients, respectively. The incidence of 2-year total and extensive chronic GVHD was 38% and 19%, respectively. The 2- and 5-year cumulative incidence of non-relapse mortality, relapse incidence, leukaemia-free survival, overall survival and GVHD-free, relapse-free survival (GRFS) were 24% and 26%, 56% and 62%, 20% and 12%, 30% and 14% and 12% & 7%, respectively. In multivariate analysis, factors associated with overall survival were age, time from allo-HCT1 to relapse, conditioning for allo-HCT1, Karnofsky score at allo-HCT2 and donor type for allo-HCT2. In conclusion, outcomes of allo-HCT2 in ALL patients were poor, with only 14% overall survival and 7% GRFS at 5 years with very high relapse incidence.     

Prognostic Importance of Morphology (FAB Classification) in Childhood Acute Lymphoblastic Leukaemia (ALL)

S ummary. The French-American-British (FAB) classification has been proposed as a useful and uniform method of defining morphologic subsets of acute leukaemias. As part of a prospective study designed to identify subsets of children with high risk of early relapse (CCG 141), submitted bone marrow slides from 765 of 883 patients entered on study were reviewed by two morphologists blinded as to prognostic factors and treatment regimen. L₁, L₂ and L₃ acute lymphoblastic leukaemia (ALL) comprised 85·1%, 14·1% and 0·8%, respectively, of the total population. Children with > 25% L₂ lymphoblasts had a significantly higher relapse rate and significantly poorer survival. Results of this study indicate that as a single variable, lymphoblast morphology is a very significant predictor of survival, haematologic remission, and complete continuous remission. Multivariate analyses show that lymphoblast morphology is again significant in determining duration of survival ( P =0·048), and is of borderline statistical significance ( P =0·089) in predicting length of complete continuous remission. The FAB classification, with minor modifications, is reproducible, useful, and prognostic in childhood ALL.     

Similar outcome of upfront‐unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party,Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first‐line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second‐line therapy with unrelated donor HSCT post‐failed IST (n = 24). The 2‐year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post‐IST failure controls (P = 0·02).The 2‐year event‐free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post‐IST failure controls (n = 24) (P = 0·02). Outcomes for upfront‐unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post‐IST failure. Front‐line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first‐line therapy in selected paediatric patients who lack a MSD.     

Bone marrow transplantation versus chemotherapy in the treatment of very high-risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI

The role of bone marrow transplantation (BMT) in first remission of children with high-risk acute lymphoblastic leukemia (ALL) remains unclear. There were 3676 patients (aged 1 to 15 years) entered into the United Kingdom (UK) Medical Research Council (MRC) trials UKALL X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were classified as very high (VH) risk and were eligible for a transplantation from a matched histocompatible sibling donor (MSD). We tissue-typed 286 patients; 99 patients had a matched related donor, and 76 patients received transplantations. Additionally, 25 children received transplantations from a matched unrelated donor (MUD) despite trial guidelines for MSD transplantations only. The median time to transplantation was 5 months (range, 2 to 19 months), and the median follow-up was 8 years. The 10-year event-free survival (EFS) adjusted for the time to transplantation, diagnostic white blood cell (WBC) count, Ph chromosome status, and ploidy was 6. 0% higher (95% confidence interval (CI), -10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD) than for the 351 patients treated with chemotherapy (transplantation, 45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer relapses (31%) compared to relapses in the chemotherapy group (55%); however, the transplantation group had more remission deaths (18%) compared to remission deaths in the chemotherapy group (3%). In contrast the adjusted 10-year EFS was 10. 7% higher (95% CI, -2.6% to 24.0%) for patients without a human leukocyte antigen (HLA)-matched donor than for those patients with a donor (no donor, 50.4%, vs donor, 39.7%). In conclusion, for the majority of children with VH-risk ALL, the first-remission transplantation has not improved EFS.     

Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG)

This retrospective survey of the EBMT Leukaemia Working Party describes 78 patients with myelodysplasia (MDS) or secondary acute myelogenous leukaemia (sAML) who received an allogeneic bone marrow transplant (BMT). The status of underlying disease at the time of transplantation was prognostic for the 2-year disease-free survival. Thirty-four patients received intensive chemotherapy prior to the conditioning for BMT. The 2-year disease-free survival was 60% for the 16 patients transplanted in complete remission. The results were significantly less favourable for those with more advanced disease who only partially responded to prior intensive chemotherapy (2-year disease-free survival: 18%) while none of those who either relapsed or were resistant to chemotherapy survived BMT for 2 years. Forty-four patients had not received any prior intensive chemotherapy. The disease-free survival at 2 years after BMT was 58 +/- 19% when a patient was transplanted for refractory anaemia (RA(S], 74 +/- 14% for refractory anaemia with excess of blasts (RAEB), 50 +/- 16% for RAEB in transformation (RAEBt), and 18 +/- 11% for secondary AML. Allogeneic BMT can therefore be considered as curative treatment for patients with MDS. Patients with sAML who have a histocompatible donor should be given chemotherapy intensive enough to induce complete remission. If this is achieved these individuals have a prognosis comparable to those with de novo AML in first remission after BMT.     

Peripheral blood stem cell (PBSC) mobilization and transplantation after fludarabine therapy in chronic lymphocytic leukaemia (CLL): a report of the European Blood and Marrow Transplantation (EBMT) CLL subcommittee on behalf of the EBMT Chronic Leukaemias Working Party (CLWP)

We performed a survey from 122 centres of the European Group of Blood and Marrow Transplantation (EBMT) concerning peripheral blood stem cell (PBSC) mobilization after fludarabine treatment of patients with chronic lymphocytic leukaemia (CLL). A total of 101 leucaphereses from 29 patients was performed. The median cell numbers collected were: CD34+ cells, 2.2 x 106/kg (0.1-15.3); granulocyte-macrophage colony-forming units (GM-CFU), 4.29 x 104/kg (0.4-177); and mononuclear cells, 6.4 x 108/kg (1.3-63). In univariate and multivariate analyses, the numbers of cells collected were not significantly influenced by the nature of mobilizing regimen and there was a trend towards the collection of a higher number of CD34+ cells from patients who received fludarabine only before mobilization. There was a significant correlation between the median number of CD34+ cells collected and the number of courses of fludarabine (higher CD34+ cell numbers were related to more than six courses) and the interval between the last dose of fludarabine and the start of mobilizing therapy (higher CD34+ cell numbers were related to a delay > or = 2 months). Sixteen patients have subsequently undergone autologous transplantation and showed rapid engraftment. In conclusion, the results reported favour early stem cell mobilization in CLL patients who are in remission after first-line therapy. However, attention should be given to the timing of mobilization with respect to the time since the last dose of fludarabine.     

Analysis of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study

The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study is the first nationally representative survey of diabetes in India. It aims to provide national and regional counts of diabetes and prediabetes and also of cardiovascular risk factors. This ambitious and complex survey uses robust sampling techniques, standardized methods, appropriate quality assurance, and a three-phase data collection. However, the survey should be completed within a reasonable time span to avoid a differential effect of secular trends on regional estimates. A high response rate and low missing values must also be ensured. Reliance on capillary whole blood glucose (CBG) for the diagnosis of hyperglycemic states is a limitation of the survey. However, this is a reasonable compromise given the practical challenges of such a large study. Despite a good correlation between CBG and venous plasma glucose (VPG), the use of CBG may misclassify glycemic status. A better characterization of the CBG-VPG relationship, and the performance of CBG for detecting hyperglycemia, using a much larger sample, seems therefore advisable. This should be possible given that venous blood has been collected on a sizeable subset of participants. The Indian Council of Medical Research and the Madras Diabetes Research Foundation deserve praise for this massive undertaking, which will highlight areas for policy action and establish a national framework for noncommunicable disease (NCD) surveillance. The ICMR-INDIAB survey lays the foundation for effective NCD prevention and control and for applied public health research.     

Phase II Trial of Prednimustine®, Leo-1031 (NSC-134087) in Acute Non-Lymphocytic Leukaemia

18 patients with acute non-lymphocytic leukaemia were treated with Prednimustine, a chlorambucil ester of prednisolone, as a single drug. 5 patients responded with falling blast counts in peripheral blood, but only 1 obtained a complete remission of 3 months' duration. Since the activity of Prednimustine is lower than that of other commonly used drugs in acute non-lymphocytic leukaemia, future studies should concentrate on other aspects, such as treatment of patients with steroid receptor-positive blast cells or other types of leukaemia.