Poor outlook for childhood acute lymphoblastic leukaemia with relapse.

Results of treatment in 72 children with a relapse of acute lymphoblastic leukaemia were analysed. A second remission was induced in 57 children (79%). Remission rates were significantly higher in males, and in patients with white cell counts less than 30 X 10(9)/L. The median duration of the second remission was only four months, and the median duration of survival from the time of relapse was nine months. The median duration of survival from the time of diagnosis was 27 months. Among children who suffered a relapse was a small group who had prolonged survival and prolonged second remissions. It is uncertain whether some of these may have a chance of "cure".     

Bone marrow Th2 cytokine expression as predictor for relapse in childhood acute lymphoblastic leukemia (ALL)

The immunological environment of leukemic blasts in the bone marrow might play a decisive role in determining an individual's risk for relapse. In order to identify potential predictors of relapse and to elucidate the mechanisms of immune control of leukemic blasts we examined the expression of cytokines, costimulatory molecules and members of the TNF family in leukemic marrow samples in a prospective study. Samples from 49 consecutive pediatric patients with B cell precursor acute lymphocytic leukemia (BCP ALL) were analyzed by semiquantitative RT-PCR. We identified interleukin (IL)-10 expression as a significant adverse prognostic indicator in childhood BCP-ALL. The event free survival (EFS) of patients expressing IL-10 mRNA in high quantity was significantly lower compared with patients expressing low IL-10 mRNA. Taqman RT-PCR of sorted cell populations showed that IL-10 mRNA was synthetized almost exclusively by NK or T cells. In addition, we found an increased expression of IL-1, IL-4, CD86 and VEGF mRNA in patients with late relapses. Possibly, ALL cells mediate a Th2 shift through increased expression of CD86 and thereby influence the individual relapse risk. These findings emphasize the role of the immune system for the outcome of childhood ALL.     

Uterine and ovarian leukaemic relapse during bone marrow remission in acute lymphoblastic leukaemia.

A patient with acute lymphoblastic leukaemia who developed ovarian and uterine leukaemic relapse while in bone marrow remission is described. Pelvic relapse is rarely reported during the clinical course of leukaemia in females. Pelvic ultrasonography, a non-invasive procedure, was of value as an aid in detecting pelvic relapse.     

Prognostic factors in childhood acute lymphoblastic leukaemia

58 patients under the age of 14 years with acute lymphoblastic leukaemia were managed from 1971 to 1985. We analysed their overall survival from diagnosis to assess the prognostic significance of clinical and laboratory features presentatdiagnosis. Factors which were statistically significant included white blood count, platelet count, palpable lymph node enlargement, mediastinal widening on chest x-ray and palpable splenic enlargement The purpose of this study was to identify that subset of patients which might have benefitted from more intensive treatment.     

Medical cost of curing childhood acute lymphoblastic leukaemia

Between 1970 and 1979 acute lymphoblastic leukaemia was diagnosed in 378 children at this hospital. The outcome for the 181 survivors was examined six or more years after diagnosis to assess morbidity in an unselected group of long term survivors. One hundred and thirty seven of the survivors were in first remission and probably cured (group I). Forty four (group II) had had one or more relapses, some of whom, who had isolated extramedullary relapses, also have a good chance of cure. In group I 136 patients had prophylactic cranial or craniospinal irradiation, while patients in group II, in addition to having that treatment, received local testicular (17) or craniospinal radiation (seven) for testicular or central nervous system relapse. Eight had additional prophylactic cranial radiotherapy after bone marrow relapse, and six had total body irradiation before bone marrow transplantation. The incidence of clinically important growth and endocrine morbidity was 20% in group I and 68% in group II. The morbidity in patients in group I was mainly attributable to early pubertal maturation. In group II 30 patients had growth failure, of whom 19 had gonadal failure from testicular or total body irradiation, 14 had growth hormone deficiency after doses of cranial irradiation of over 2400 cGy, and 10 had spinal growth impairment after craniospinal irradiation. Two also had early pubertal maturation. Five out of six patients who received total body irradiation had multiple endocrine deficiency. Neuropsychological sequelae of treatment were seen in 40 (42%) of 96 schoolchildren in group I and in 12 (38%) of 32 schoolchildren in group II. Postinfective sequelae of treatment were found in patients in both groups. These results show that the survivors who were in their first remission had a 42% residual morbidity related to treatment compared with an 82% morbidity in the survivors of one or more relapses who had multiple treatments.     

Epidemiology of acute lymphoblastic leukaemia of childhood in Brisbane

The incidence of acute lymphoblastic leukaemia of childhood in the Brisbane Statistical Division has been studied. Sixty-four cases occurred during a five-year period. A significant difference between the two subdivisions of the Statistical Division was found, with a higher incidence in Brisbane City than in the surrounding area. The average age at presentation of the leukaemic children within Brisbane City was significantly higher than in the rest of the Brisbane Statistical Division. Various socioeconomic and demographic differences exist between the two populations, and these may be responsible for the variation in leukaemia incidence. The findings indicate the need for further, more detailed, epidemiological studies.     

Bone marrow transplantation for acute myeloblastic leukemia.

Fifty-seven patients with end-stage acute myeloblastic leukemia (AML) received a total of 65 bone marrow transplants between 1968 and 1976. Marrow from HLA genotypically identical allogeneic donors was administered to 32 patients, 13 received marrow from HLA-incompatible donors, donor-recipient HLA compatibility was undetermined for eight patients, and identical twins were marrow donors for four patients. None of the patients in the three latter groups survived beyond 9.4 months after transplantation. Two patients treated with marrow transplants from HLA-compatible donors currently are alive and free of leukemia with functioning grafts 13 and 38 months after transplantation. The 32 patients in the Registry series who received marrow from HLA-compatible donors were compared with a similar series of 46 patients in Seattle. Data for these 78 patients were pooled and analyzed for pretransplant factors that might have prognostic value. Patients with end-stage AML had approximately a 10% chance of surviving 20 months after high-dose chemoradiotherapy plus marrow transplantation. Patients younger than 21 years had a higher six-month survival rate than patients older than 30 years. Patients in the Registry series who received transplants with HLA-compatible marrow within eight months of diagnosis had a higher survival experience than patients who received transplants later.     

急性淋巴细胞性白血病外周血干细胞移植术后单纯髓外眼部复发

Isolated extramedullary ocular relapse of acute lymphoblastic leukemia （ALL） after allogeneic peripheral blood-stem cell transplantation （allo-P-BSCT） without concomitant involvement of the bone marrow is very rare,while the common sites of extramedullary relapse are the central nervous system, skin, bone, and breasts.^1 This is the report of isolated ocular relapse without any extra- ocular involvement of ALL after allo-PBSCT confirmed by histopathology.     

Relapse of acute lymphoblastic leukemia in the pancreas after allogeneic bone marrow transplantation

The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon （1.6%-37.5%） and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,     

Recent experience with intensive combination chemotherapy for treatment of childhood acute lymphoblastic leukaemia

Forty-eight children with acute lymphoblastic leukaemia (ALL) who presented to the Oncology Department of Our Lady’s Hospital for Sick Children, Crumlin, Dublin over a 52 month period were treated using a schedule modified from the BFM-81 protocol. All patients achieved remission within four weeks. With a minimum follow up period of 18 months, actuarial disease free survival was 68% and overall survival 75%. Mean hospital stay throughout the treatment period was 31 days. While these results represent an improvement in overall survival compared with historical controls, careful selection of risk categories will be the major aim of future studies so that more appropriate treatment can be instituted for high risk patients while minimising therapy for low risk disease.     

Hypercalcaemia and multiple osteolytic lesions in childhood acute lymphoblastic leukaemia.

A 12 year old boy presenting with hypercalcaemia (calcium 3.25 mmol/l) and osteopaenia with multiple osteolytic lesions was found to have acute lymphoblastic leukaemia without lymph-adenopathy or organomegaly. Hypercalcaemia is a rare feature of acute leukaemia, but the patients previously described all show very similar characteristics, which were highlighted in this patient. These include age (10-20 years), severe osteolytic bone lesions, lymphoblastic leukaemia, and normal white cell count with absent or rare circulating blasts. Parathyroid hormone levels were normal in this patient, and response to induction therapy was good. This case demonstrates that acute lymphoblastic leukaemia may present in an atypical form without peripheral blasts but with hypercalcaemia and gross skeletal changes.     

Bone marrow transplantation.

Over the last 20 years allogeneic bone marrow transplantation from an HLA-identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer.