The common chromosome abnormalities that are encountered in the various types of leukemia are discussed here. Chromosome abnormalities in leukemia are non-random and certain chromosomal changes are now becoming recognised as being rather specific for certain leukemia types.
Acute leukaemia may rarely present as diffuse papules, nodules and plaques forming leonine facies. Leukaemia cutis generally carries a poor prognosis, and responds less well to chemotherapy. We described a case of acute myelomonocytic leukaemia presenting as leonine facies as a result of extensive cutaneous infiltration. The patient did not achieve haematological remission following standard induction chemotherapy and succumbed 6 weeks after the diagnosis was made.
Most methods used in double esterase cytochemistry for the diagnosis and classification of acute myeloid leukaemias require double incubation and staining, using separate coupling reagents. We evaluated a method by Swirsky on our normal and abnormal blood and bone marrow smears where only a single incubation and the use of a single coupling reagent is required. Its short incubation period and its strong positive reaction for butyrate esterase in demonstrating cells of monocytic lineage gives it an advantage over the conventional double incubation technique.
The first cooperative study of the Asian Pacific bone marrow transplantation group included 75 patients with early leukemia who received human leukocyte antigen-matched sibling bone marrow transplants and were randomized into granulocyte colony-stimulating factor and control groups. The selected patients were registered from 10 centers in six countries and areas within Asia (Beijing, Taipei, Hong Kong, Japan, Korea, and Malaysia). The incidence of grades II-IV acute graft-vs.-host disease was 22.2%, and the 2-year survival rate was 62.7%. The period of protective isolation (27.1-66.7 days), period of hospitalization (38.6-130.5 days), and medical costs for 4 months (US $10,300-US $80,803) varied considerably. Good cooperation, i.e., low rate of protocol violation or rapid and precise presentation of case reports, was obtained.
Congenital leukaemia which is characterised by proliferation and extrahaemopoietic infiltration of immature leucocyte precursor cells is a rare disorder encountered in the neonatal period. Although more than 100 cases of congenital leukaemia have been reported in the literature, the experience of most general paediatricians with this condition is very likely to be limited. Thus a patient presenting with congenital leukaemia admitted to Alor Star General Hospital is reported.
The simultaneous expression of both lymphoid and myeloid phenotypic features in acute leukaemia is rare. We report 3 cases of biphenotypic hybrid acute leukaemia seen in our institution. All 3 patients achieved remission with treatment for acute lymphoblastic leukaemia but two subsequently relapsed while on treatment. The hybrid acute leukaemias are important areas for further research both for delineation of basic biology and choice of optimal treatment.
This study reviewed the immunophenotyping results of children with acute leukemia in Kelantan, Malaysia. In the 3.5-year period (January 1994 to June 1997), 45 cases were identified. All children were under the age of 12 years and the predominant ethnic group was Malay. Thirty-six cases (80%) were acute lymphoblastic leukemia (ALL) and 9 cases (20%) were acute myeloblastic leukemia (AML). Of the ALL cases, 3% were of B-cell and 22% of T-cell origin, and 96% of the B-lineage ALL were CD10 positive. All the AML cases expressed CD33 and 78% were positive for CD13. The incidence of mixed-lineage leukemias was 13.8% for My+ ALL and 11.1% for Ly+ AML.
A female Malay patient with acute lymphoblastic leukemia in remission for one year developed bilateral visual loss. The ophthalmoscopic appearance showed infiltration of optic nerves and retinae by leukemic cells. At that time, her blood, bone marrow and cerebral spinal fluid remained normal. She had received prophylactic cranial irradiation and intrathecal methotrexate as part of the treatment programme. It was likely therefore she had a leukemic relapse from a pharmacologic sanctuary in the eyes. She responded to local irradiation but did not regain her sight. Three months later, she had a bone marrow relapse.
Objective: Despite much progress in treatment strategies, long term survival of adult ALL is still inferior to that in children. The underlying mechanisms for these differences are largely unknown. Intensification of contemporary therapy has also resulted in many children being over-treated. The action of chemotherapeutic drugs used in the treatment of ALL includes cell cycle dependent agents which are effective on cells that are proliferating. Cell proliferation in haemopoietic cells is controlled by cytokines. Thus, we proposed to study the cell cycle profile of ALL cases and also expression of cytokines to determine their role in affecting treatment outcome in the different age groups.
Methods: We determined the S-phase fraction from the cell cycle profile by flowcytometry and tested the expressions of cytokine IL-1beta, IL-6, IL-18, IFN-gamma, TNF-alpha and GM-CSF using RT-PCR in de novo ALL cases.
Results: We found a significantly higher S-phase fraction in samples from children 2-10 years old compared to the older age group (>10 years old) (p=0.001). GM-CSF was found to be expressed in a significantly lower percentage of children compared to adults (p=0.008).
Conclusion: Our results implied that GM-CSF may have induced cell cycle arrests in adult ALL resulting in a lower percentage of S-phase fraction. This may contribute to the poorer prognosis in adult ALL because non-cycling blasts are less sensitive to some chemotherapeutic drugs.
Keywords: ALL, S-phase fraction, GM-CSF, age
Immunophenotypic studies using immunofluorescent flow cytometry were performed on the blast cells of 36 patients with acute leukaemia using a panel of eight monoclonal antibodies. Six patients had blasts which co-expressed markers for lymphoid and myeloid differentiation, and which were therefore defined as biphenotypic hybrid acute leukaemia. Of the six, three patients were in the paediatric age group (below 12 years old) while the other three were more than 12 years old. Peripheral blood counts were variable; however, bone marrow infiltration was extensive (blasts > or = 75% in all). At the time of study, remission was achieved in only two patients. The authors' data show that biphenotypic hybrid acute leukaemia is not rare in Malaysia. This represents a subgroup of acute leukaemia identifiable by immunophenotyping but not by the French-American-British classification based on morphological and basic cytochemical studies alone. The recognition of this subgroup is important for both practical and theoretical reasons. There are implications for treatment of the individual patient because treatment directed at a single lineage may not be effective. The two colour flow cytometry proved to be a useful tool for diagnosis and classification of acute leukaemia.
This study aimed to assess the physical activity levels of pediatric patients with acute leukemia undergoing chemotherapy. Thirty-eight pediatric patients and matched controls, aged 3-12 years old, were measured for weight, height, and other anthropometric parameters. Physical activity was assessed using actical accelerometer and activity log book. Patients recorded significantly lower mean total activity counts (26.2±30.2 cpm vs. 192.2±68.8 cpm; p<0.01) and spent more time in sedentary activities (1301±121 min vs. 1020±101 min; p<0.001) compared to controls. They also achieved fewer 1-5-min bouts of moderate-vigorous physical activity (MVPA) compared to controls (1.50±5.95 vs. 37.38±40.36; p<0.001). In conclusion, patients had lower physical activity level and intensity; and simple exercise intervention programs may be needed to minimize the detrimental effects of prolonged sedentary behaviors.
The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.
The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
Retinal changes are common in adult acute leukemia patients at presentation, but their prognostic significance is controversial. A 5-year study has been carried out with newly diagnosed acute leukemia patients aged 12-77 years. Seventy-seven cases (49 AML, 28 ALL) were studied prospectively for the presence of intraretinal hemorrhages (IRH), white-centered hemorrhages, cotton-wool spots, and macular hemorrhages. They were treated according to standard chemotherapy protocols, and then achievement of complete remission (CR) and the duration of overall survival (OS) were compared between the groups with and without these different retinal features. No association was found between the presence of any retinal abnormality and CR induction rate, although there was a trend to a lower CR rate among patients with IRH. The median OS of those with IRH was 72 days, compared with 345 days among those without IRH (p=0.002). A WBC at presentation greater than 50x10(9)/l and age greater than 40 years were also associated with shorter OS (p<0.0001 and p=0.0045, respectively). However, after regression analysis, IRH remained statistically significant as a poor prognostic indicator (p=0.01). We conclude that the presence of IRH is an indicator of poor prognosis in acute leukemia.