Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.     

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.     

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.     

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.     

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.     

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.     

利妥昔与DC-CIK治疗ALL患儿的疗效及预后影响分析

目的 研究利妥昔配合DC-CIK治疗儿童前体B型急性淋巴细胞白血病（ALL）的疗效及不良反应,重点分析利妥昔对DC-CIK治疗后的影响。方法 回顾分析2006年6月—2012年6月四川省遂宁市中心医院50例CD20阳性的ALL患儿,分为对照组和观察组,每组25例。对照组采用化疗配合DC-CIK治疗;观察组采用利妥昔、化疗和DC-CIK联合治疗的方法。比较两组患儿治疗后的临床疗效及不良反应,并统计随访中两组患儿的3年无事件生存率。结果 治疗后两组患儿Per2、Bmal1及EVI1 mRNA比较,差异有统计学意义（P?<0.05）,表达下降,且观察组低于对照组。观察组与对照组比较,治疗后临床疗效略好,但其不良反应较多。观察组患儿3年无事件生存率高于对照组。结论 利妥昔配合DC-CIK治疗疗效更佳,利妥昔对DC-CIK预后有促进作用,但其治疗后副作用较多且费用较高。     

Aspergillosis in a patient with acute lymphoblastic leukaemia

A case is described of a 3-year-old boy with acute lymphoblastic leukaemia (ALL) who presented initially with aspergillosis of the nasopharynx. Fungal infection with Aspergillus species is not uncommon in immunosuppressed children, but this case is noteworth in that the disease presented at the onset of therapy rather than during the phase of treatment, with maximum immunosuppression following chemotherapy. This type of infection is usually associated with the treatment of acute non-lymphoblastic leukaemias (AML) rather than ALL, and prolonged periods of neutropenia which results from aggressive treatment. This patient responded rapidly to treatment with amphotericin B, coincident with resolution of his neutropenia as the underlying disease was treated, eventually eradicating the fungus.     

Haemophagocytic syndrome complicating acute lymphoblastic leukaemia

A 41 year old female developed reactive haemophagocytic histiocytosis secondary to herpes simplex infection, during remission induction for acute lymphoblastic leukaemia. She recovered fully with acyclovir and supportive treatment. Previous publications on the association between acute lymphoblastic leukaemia and haemophagocytic syndrome are reviewed, and the nature of the haemophagocytic disorder is discussed.     

Adult acute lymphoblastic leukaemia: a five-year experience.

The case histories of all patients for whom the diagnosis of acute lymphoblastic leukaemia (ALL) was made over a five-year period at the Royal Adelaide Hospital and Institute of Medical and Veterinary Science were studied. There were 34 patients with a median age of 47.5 years. Adequate follow-up was obtained on 33 patients, and their median survival was 5.4 months. The remission rate was 77% in the under-30 years age group, but only 15% in the over-30 years age group. The median duration of remission was 24 months while the median survival of remitters has not yet been reached. The median survival of non-remitters was two months with 100% being dead at 12-3 months. Of 20 patients without remission, seven died of haemorrhage and/or infection before an adequate trial of therapy had been completed, while nine patients had "adequate" intensive therapy but failed to achieve remission.     

Long term survivors following treatment of childhood acute lymphoblastic leukaemia during 1970–75

TWENTY-THREE patients were treated for childhood acute lymphoblastic leukaemia during 1970–1975 in the National Children’s Hospital, Dublin. Twelve patients (52%) were alive and in first remission five years after diagnosis. One patient relapsed nine years after diagnosis; the remainder, 48%, are alive and in first remission between 12 and 17 years after diagnosis. Our experience is similar to the results reported from the more successful larger centres in other countries.     

Hodgkin's disease in an adult with acute lymphoblastic leukaemia

A 53 year old woman with common acute lymphoblastic leukaemia (ALL) developed Hodgkin's disease 20 months after the initial diagnosis of ALL. This is by far the oldest case of Hodgkin's disease complicating ALL. The unusual presentation and the aetiology of Hodgkin's disease in ALL are discussed.     

Invasive aspergillosis in two patients with acute lymphoblastic leukaemia in complete remission.

Invasive aspergillosis is a disease of the immunosuppressed patient. We describe two patients with acute lymphoblastic leukaemia who attained complete remission, with partial or complete bone marrow recovery, but who went on to develop fatal invasive aspergillosis contemporaneous with recovery of neutrophil counts. Quantitative recovery of peripheral blood neutrophil counts does not guarantee control of Aspergillus infection, perhaps due to functional neutrophil deficiencies post-chemotherapy, and specific defensive strategies adopted by the organism itself.     

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.