Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression

Biphenotypic acute leukaemia (BAL) patients represented 8% of the 287 de novo consecutive adult acute leukaemias (23 BAL, 230 acute myeloid leukaemia (AML) and 34 acute lymphoblastic leukaemia (ALL)) referred to our department during the last 4-year period. Of these 23 BAL patients, 14 patients showed myeloid morphology and nine cases lymphoid morphology according to FAB criteria. There were no differences between lymphoid and myeloid BAL according to clinical and biological presentation and treatment outcome. We confirm the poor prognosis of BAL when compared to AML or ALL seen during the same period of time, in terms of complete remission (47%, 62% and 82% respectively, BAL v AML, NS and BAL v ALL, P  = 0.006) and 4-year overall survival (8.1%, 25.8% and 23.8% respectively, BAL v AML, P  = 0.05 and BAL v ALL, P  = 0.003). Comparing adult BAL patients with AML patients, we found an increase in poor prognostic factors: CD34⁺ phenotype (82% v 60% respectively, P  = 0.03), unfavourable karyotype (60% v 20%, P  < 0.0001) and Pgp over-expression by RT-PCR (0.705 v 0.107, P  < 0.0001) and flow cytometry (0.824 v 0.391, P  = 0.0001). MRP and LRP were not found to be poor prognostic factors. Comparing BAL patients with ALL patients, we found also an increase in poor prognostic factors: age (51 v 39, P  = 0.003) and CD34⁺ phenotype (82% v 50%, P  = 0.02). We conclude that BAL patients need a more aggressive treatment procedure, including high-dose AraC or the use of Pgp modulators for first-line therapy.     

Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison

Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML.     

Vinorelbine-based salvage chemotherapy for therapy-refractory aggressive leukaemias

This study examined the ability of the semi-synthetic vinca alkaloid, Vinorelbine/Navelbine, to cause apoptotic death in freshly obtained primary leukaemia cells from 53 patients with haematological malignancies, including 22 patients with acute lymphoblastic leukaemia (ALL), 24 patients with chronic lymphocytic leukaemia (CLL), three patients with chronic myeloid leukaemia in blast crisis (CML-BC) and four patients with acute myeloid leukaemia (AML). Vinorelbine caused apoptosis in primary leukaemia cells from 42 (79%) of these leukaemia patients. Objective responses, including complete remission (CR) and CR with incomplete haematological recovery, were achieved in 12 of 17 (71%) patients with aggressive and therapy-refractory leukaemias, including five of nine patients with relapsed ALL, three of three patients with CML-BC and four of five patients with rapidly progressive CLL, who were treated with a vinorelbine-based salvage chemotherapy regimen. Drug sensitivity profiling of multidrug-resistant primary cancer cells using apoptosis assays revealed a significant association between Vinorelbine sensitivity in vitro and the likelihood of an objective clinical response to Vinorelbine-based chemotherapy. Vinorelbine-sensitivity testing of primary leukaemia cells might help tailor Vinorelbine-based salvage regimens to those patients who are most likely to respond.     

Acute leukaemia in children with Down syndrome: a population-based Nordic study

To determine the epidemiology and outcome of children with Down syndrome (DS) diagnosed with acute leukaemia in the Nordic countries, data registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) population-based leukaemia registry were analysed. Of 3494 children with acute leukaemia diagnosed between July 1984 and December 2001, 136 patients (3.9%) with DS were identified. 2.1% of the children with acute lymphoid leukaemia (ALL) and 14.0% of the children with acute myeloid leukaemia (AML) had DS. In ALL, DS patients had similar age and sex distribution and no major differences in blood counts compared with non-DS children. None of the DS patients had T cell leukaemia. Outcome was inferior to that of non-DS children and treatment results did not improve over time. In AML, DS patients showed a significant female predominance and all but one were <5 years old. DS patients with AML had significantly lower platelet and white blood cell counts and two-thirds were type M7 as according to the French-American-British classification. None of the patients <5 years of age had typical AML cytogenetic aberrations. Outcome was far better in the DS group. DS patients treated for AML after 1992 had an excellent outcome (probability of event-free survival, 83 +/- 6%). The high proportion of female DS patients with AML is unexplained. The differing treatment results in AML versus ALL need further evaluation and represent a challenge for the coming years.     

Haematologists' approaches to the management of adolescents and young adults with acute leukaemia

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.     

Survival in adult leukaemia

Summary The evaluation of treatment and outcome in adult leukaemia requires unselected data. Such data is available from one Health Region in the United Kindgom with an adult population of 3.1 million. In the period July 1982 to December 1989, 676 cases of acute myeloid leukaemia (AML), 136 of acute lymphoblastic leukaemia (ALL) and 141 of chronic granulocytic leukaemia (CGL) were registered. The median survival for AML was 21 weeks and 26% of these patients died within 4 weeks of diagnosis. For ALL, the corresponding figures were 81 weeks and 21%. In CGL, the median survival was significantly different for males and females: 113 weeks and 173 weeks respectively. The 5-year survival in AML was 9%, in ALL, 31% and in CGL, 29% (20% for males, 45% for females). Age at presentation was the single most powerful prognostic factor and probably accounts for survival differences between patients referred to tertiary centres and those treated in district general hospitals. (DGH). Survival may be improving overall as supportive care improves.     

Survival in adult leukaemia.

The evaluation of treatment and outcome in adult leukaemia requires unselected data. Such data is available from one Health Region in the United Kingdom with an adult population of 3.1 million. In the period July 1982 to December 1989, 676 cases of acute myeloid leukaemia (AML), 136 of acute lymphoblastic leukaemia (ALL) and 141 of chronic granulocytic leukaemia (CGL) were registered. The median survival for AML was 21 weeks and 26% of these patients died within 4 weeks of diagnosis. For ALL, the corresponding figures were 81 weeks and 21%. In CGL, the median survival was significantly different for males and females: 113 weeks and 173 weeks respectively. The 5-year survival in AML was 9%, in ALL, 31% and in CGL, 29% (20% for males, 45% for females). Age at presentation was the single most powerful prognostic factor and probably accounts for survival differences between patients referred to tertiary centres and those treated in district general hospitals. (DGH). Survival may be improving overall as supportive care improves.     

Congenital leukaemia: the Dutch experience and review of the literature

We reviewed Dutch patients and those described in the literature with congenital leukaemia in the past 25 years, with the intention to obtain an overview of the characteristics of this rare disease. Among the 117 patients reviewed, acute myeloid leukaemia (AML) was more frequent (64%) than acute lymphoblastic leukaemia (ALL, 21%). Most patients had a high leukaemic cell load with hepatosplenomegaly, leukaemia cutis and hyperleucocytosis. Cytogenetic abnormalities were found in the majority of the patients tested (72%); 11q23 abnormalities were found in less than half of them (42%). The probability of overall survival at 24 months was only 23%. When congenital AML and ALL were compared, clinical characteristics and overall survival were not significantly different. However, in patients at risk, the probability of event-free survival (EFS) and disease-free survival (DFS) were significantly higher in AML than in ALL, 43% versus 13% and 68% versus 0% respectively. Among the congenital AML cases, six spontaneous remissions have been described. In conclusion, the clinical characteristics of congenital leukaemia differ from those of leukaemia in older children and prognosis is generally poor. Once complete remission is achieved, patients with AML fare better than those with ALL. Chemotherapy for congenital leukaemia needs improvement to increase the sustained remission rate.     

Impaired granulocytic function in patients with acute leukaemia: only partial normalisation after successful remission-inducing treatment

In vivo chemotaxis and phagocytic activity of polymorphonuclear neutrophils (PMN) were evaluated in 20 patients with acute myeloid leukaemia (AML), and in 10 patients with acute lymphoblastic leukaemia (ALL). For comparison, 20 healthy individuals were investigated. A skin-chamber technique and a phagocytosis test were used to quantify the neutrophil functions. The local leucocyte mobilisation in the skin- chamber was significantly lower in untreated patients with AML and ALL than in healthy individuals (P<0.05). Patients with acute leukaemia in remission showed an increase in chemotactic parameters though they remained below normal levels. The phagocytosis index (PI) of peripheral blood PMN was lower than 30% (normal individuals: 60%) in untreated AML and ALL; this difference was significant (P<0.05). The PI of peripheral blood PMN in patients with acute leukaemia in remission returned to the normal level. Investigation of granulocytic function in patients with acute leukaemia in remission may reveal evidence for reduced protection by these cells against infections and lead to adequate therapy. Received: 20 November 1997 / Accepted: 9 December 1997     

Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5-year survival of 18%. 28% of patients died of transplant-related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi-factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre-transplant variables significantly associated with improved survival. Acute graft-versus-host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I-II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5-year survival > 20%. Transplants for AML in induction failure or pre-B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5-year survival of 10-20%. A 5-year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre-B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.     

Chromosome Banding Studies in Acute Leukaemia at Diagnosis

Cytogenetic study by a chromosome banding technique has been attempted in 93 cases of acute leukaemia at diagnosis. Banding patterns were difficult to visualise in the bone-marrow chromosomes of patients with acute leukaemia because of the fuzzy appearance of the fixed metaphases. The proportion of patients with abnormal chromosomes was higher in acute lymphoblastic (ALL) than in acute myeloid (AML) leukaemia. Abnormalities were present in all cases of other cytological types. Hyperdiploidy was the most commonly found numerical error in both ALL and AML but a larger proportion of patients with ALL had hyperdiploidy in more than 30% of the cells. In ALL it was generally found that the higher the frequency of hyperdiploidy the greater was the number of chromosomes per cell. Hypodiploidy not attributable to random losses was found in only 6 patients. Clones identified by rearranged or marker chromosomes were found in all types of leukaemia. Clones marked by a 7q-chromosome, in which the break point was the same, were identified in 1 adult with ALL and 2 children with AML. The high frequency of randomly distributed chromosomal breakage found in the bone-marrow chromosomes of a high proportion of the patients may be related to the disease process.     

The role of an anti-myeloperoxidase antibody in the diagnosis and classification of acute leukaemia: a comparison with light and electron microscopy cytochemistry

The enzyme myeloperoxidase (MPO) is the hallmark of the myeloid lineage. We have analysed the presence of MPO in blasts from 180 cases of acute leukaemia (103 acute myeloid leukaemia (AML) and 77 acute lymphoid leukaemia (ALL) by means of monoclonal antibodies anti-MPO and immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase method). The aim of the study was to investigate the specificity and sensitivity of this marker compared with MPO cytochemistry by light (LM) and electron microscopy (EM), and with the expression of myeloid antigens. Anti-MPO was positive (greater than 3% blasts) in all but one of the 90 AML positive by LM cytochemistry. Of 13 AML cases negative by MPO cytochemistry, six showed 3-10% blasts reactive with anti-MPO and were also positive with antibodies to CD13 and/or CD33. The presence of MPO was confirmed in four of these by EM. The overall positivity of anti-MPO in AML was 92%. Anti-MPO was negative in all but two ALL (6% and 8% positive blasts). The blasts in these two cases were also CD13, CD33 and MPO positive by EM; both were thus reclassified as biphenotypic. Another two ALL reinterpreted as biphenotypic were negative by MPO cytochemistry and anti-MPO but were MPO positive by EM and with CD13 and/or CD33. We conclude that anti-MPO is a sensitive and specific early marker of myeloid blasts and should be incorporated in the routine immunophenotyping of acute leukaemia.     

Long-term survival and late relapses in acute leukaemia in adults

34 out of 403 apparently unselected adult patients with acute leukaemia referred to a single department from 1970 through 1989 survived more than 3 years. The cumulative rate of relapse after 3 years was 39% in patients with acute myeloblastic leukaemia (AML) and 74% in patients with acute lymphoblastic leukaemia (ALL). The latest relapse was observed 75 months after diagnosis in AML and 98 months after diagnosis in ALL. 65% of the long-term survivors were able to undertake normal physical activity, 26% had decreased activity, and 9% were unable to work. 5-year survival for all patients, whether treated or not, during two successive decades was 16% versus 18% and 5% versus 6%, respectively, for ALL and AML. The departmental results were identical with population-based national results. Only in patients 15-49 years of age with AML was there evidence that more intensive treatment had led to better survival.     

Adult acute leukaemia - a retrospective study of 66 consecutive patients

Background: Advances in therapy and supportive care have improved the outlook for many patients with acute leukaemia, however elderly patients have increased treatment-related toxicity and shorter survival. Most clinical trials have selected patient populations with young median ages and it is therefore difficult to apply results to the general population where the majority of patients presenting with acute leukaemia are over 60 years. There is little information in the literature guiding appropriate treatment of these patients.
Aims: To determine the relationship between age, treatment received, and outcome in patients presenting with acute leukaemia.
Methods: A retrospective analysis was performed on all patients presenting to Prince Henry's Hospital and Monash Medical Centre with acute myeloid leukaemia (AML) or acute lymphocytic leukaemia (ALL) during a five year period.
Results: Sixty-six patients (51 - AML, 15 - ALL) presented with acute leukaemia between March 1989 and April 1994. Median patient age was 63 years; 32% of patients received supportive therapy only; 86% of patients with ALT, and 58% of patients with AML commencing remission-induction chemotherapy entered a complete remission. Median survival for patients receiving only supportive therapy was three months. Median survival in patients under 55 years was almost twice as long as patients over 55 years receiving similar treatment (AML - eight vs four months p =0.023; ALL - 3.5 vs seven months p =0.029).
Conclusions: Median survival for acute leukaemia is inversely proportional to age. Applying results from selected series to elderly patients with acute leukaemia is inappropriate.     

The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia

Summary. Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between samples obtained at relapse and those at presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P < 0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than in those who responded. The intensity of staining in cases of secondary AML was lower than that in de novo disease (P < 0.01). These results suggest that expression of bcl-2 may be an important prognostic feature in both de novo AML and in ALL, but not in secondary AML.     

Phase 1 dose-escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemias

The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enroled [28 acute myeloid leukaemia (AML), 12 acute lymphoblastic leukaemia (ALL)] in this Phase 1 dose-escalation trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for four consecutive days (CLO-CYx4). The median age was 48·5 years. The median number of prior regimens was 2 (range 1-5), and 6/40 patients (15%) had prior allogeneic haematopoietic stem cell transplant. 28/40 patients (70%) had adverse genetic features. 6/40 patients (15%) died within 60 d of induction (two infections, four progressive disease). The average time to neutrophil recovery (absolute neutrophil count ≥0·5 × 10(9) /l was 34 d, (range, 17-78). The overall response rate (ORR) was 33% (13/40), with seven complete remissions (18%), four complete remissions with incomplete recovery of blood counts (10%), and two partial remissions (5%). ORR was 25% (7/28), and 50% (6/12), for AML and ALL respectively. Notably, the clinical responses were independent of dose level. 7/17 patients (41%) exhibited CLO-mediated enhancement of CY-induced DNA, which was associated with, but not necessary for, improved clinical outcomes. In summary, the CLO-CYx4 regimen was well tolerated and had activity in patients with RRAL, especially relapsed ALL. Therefore, CLO-CYx4 can be considered a salvage therapy for adults with RRALs, and warrants further investigations.     

Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat

Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates difficulties in treating patients who are practising JW, yet nevertheless provides a significant argument against the prejudicial decision leading to evasion of treatment in these patients.     

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum during induction treatment of acute leukaemia

Granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are increasingly used to stimulate granulopoiesis in neutropenic patients but in most cases without any knowledge of the endogenous CSF-levels. With the purpose to define serum levels of GM-CSF and G-CSF during induction chemotherapy and haematological reconstitution in patients with acute leukaemia we have used enzyme-linked immunosorbent assay (ELISA) techniques to measure these growth factors in 18 patients with acute myeloid leukaemia (AML) and eight patients with acute lymphoblastic or undifferentiated leukaemia (ALL/AUL). G-CSF above 0.05 ng/ml was detected in 54% of the analysed AML samples, median 0.29 (range 0.05-2.80) ng/ml; and in 40% of analysed ALL/AUL samples, median 0.09 (range 0.05-3.00) ng/ml. In patients with AML there was a clear correlation between an elevated serum concentration of G-CSF and documented infections. On the other hand, 15/18 of the patients with acute myeloid leukaemia and 8/8 patients with ALL/AUL had non-detectable levels of GM-CSF (less than 0.10 ng/ml). Two patients had measurable levels of GM-CSF in all samples, median 0.71 (range 0.26-1.18) ng/ml and in these patients the levels successively decreased during and after chemotherapy and did not increase in response to infections. In normals detectable levels of GM-CSF were found in 2/35 individuals and G-CSF in 0/10 individuals.     

Current status of gene expression profiling in the diagnosis and management of acute leukaemia

Gene expression profiling (GEP) enables the simultaneous investigation of the expression of tens of thousands of genes and was successfully introduced in leukaemia research a decade ago. Aiming to better understand the diversity of genetic aberrations in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), pioneer studies investigated and confirmed the predictability of many cytogenetic and molecular subclasses in AML and ALL. In addition, GEP can define new prognostic subclasses within distinct leukaemia subgroups, as illustrated in AML with normal karyotype. Another approach is the development of treatment-specific sensitivity assays, which might contribute to targeted therapy studies. Finally, GEP might enable the detection of new molecular targets for therapy in patients with acute leukaemia. Meanwhile, large multicentre studies, e.g. the Microarray Innovations in LEukaemia (MILE) study, prepare for a standardised introduction of GEP in leukaemia diagnostic algorithms, aiming to translate this novel methodology into clinical routine for the benefit of patients with the complex disorders of AML and ALL.     

Unusual immunophenotypes in acute leukaemias: incidence and clinical correlations

The incidence and clinical implications of unusual patterns of expression of leucocyte differentiation antigens in acute leukaemia were assessed on 568 newly diagnosed paediatric and adult cases undergoing immunophenotyping with a panel of monoclonal antibodies at a single centre. Among patients with the precursor B (common) form of acute lymphoblastic leukaemia (ALL), the major variant seen was the group of 15 cases with expression of myeloid surface antigens. 4.5% of ALL cases tested with antibody to CD-11b were positive, 5.1% were CD-13+, and 10.8% CD-33+. All 15 patients achieved a complete remission with chemotherapy, with six of eight children and four of seven adults remaining disease free. A smaller proportion (1.5%) of precursor B ALL patients showed expression of the T lineage marker, CD-7. The only significant variant seen in the precursor T-ALL group was expression of HLA-DR antigen, which was found in five of 35 cases; although all responded to treatment, only one remains a disease-free survivor. Among patients with acute myeloid leukaemia (AML), expression of the lymphoid markers terminal transferase (TdT) and CD-7 were commonly seen (22.2% and 28.4% respectively of cases tested). Other lymphoid markers detected on AML cases were CD2 (11.1%), CD-10 (1%) and CD-19 (4.4%). These results confirm that examples of lineage infidelity are regularly seen in large series of patients with acute leukaemia. Prospective studies using uniform treatment protocols are required to establish whether these patients have significantly different disease outcomes.