Treatment of adult acute lymphoblastic leukemia with adriamycin, vincristine, and prednisone

At the present time, it is possible to achieve up to a 95% complete remission in childhood acute lymphoblastic leukemia, using the combination of vincristine and prednisone. Nevertheless, it has not been possible to reproduce these results in the adult. For this reason, a third drug, in this case adriamycin in a low dose, was added to the vincristine-prednisone combination in the treatment of adult acute lymphoblastic leukemia (ALL). Complete remission was achieved in 45 of the 50 patients (90%). The median duration of remission was 23 months and the median survival time in this group was 31 months. The complications were minimal and the tolerance was good. From the point of view of our results and others reported in the literature, we consider that the combination of vincristine, prednisone, and adriamycin is a useful method for induction of remission of adult ALL.     

Poland's syndrome with acute lymphoblastic leukemia in an adult

We report a patient with Poland's syndrome who developed acute lymphoblastic leukemia (ALL) at 28 years of age. This is the first time that such an association has been reported from outside the United States or in an adult. The relevant literature is reviewed.     

Acquired Glanzmann's thrombasthenia associated with acute lymphoblastic leukemia

Acquired Glanzmann's thrombasthenia is an uncommon event in association with leukemia. The authors describe a patient with acute lymphoblastic leukemia (ALL) who presented with severe hemorrhagic syndrome, without disseminated intravascular coagulation. The patient's course was complicated by the occurrence of severe hemorrhagic episodes, with a thrombasthenia-like profile, requiring multiple transfusions with packed red cells, platelets, and fresh-frozen plasma. Biological explorations detected anti-GPIIb/IIIa complex antibodies. The patient finally died with refractory disease and persistent bleeding. This case is the first reported of autoantibodies to GPIIb/IIIa in ALL. Such paraneoplastic syndrome is potentially responsible for severe life-threatening hemorrhage.     

Successfully treated acute lymphoblastic leukemia associated with craniopharyngioma

The authors report a 2-year-old boy with acute lymphoblastic leukemia (ALL) associated with craniopharyngioma. To our knowledge, this is the first such report. Magnetic resonance imaging showed a suprasellar tumor, an apparent cystic lesion, whereas cerebral computed tomography confirmed that the tumor exhibited calcification. Without surgical intervention for the suprasellar tumor, we initiated chemotherapy for ALL. After 1 year of chemotherapy, complete remission was achieved, and partial resection and radiation therapy were performed on the suprasellar tumor. At 4 years after completing leukemia chemotherapy, the patient remains in complete ALL remission and has had no recurrence of craniopharyngioma.     

Hemophagocytic lymphohistiocytosis associated with precursor B acute lymphoblastic leukemia

We report a case of a child with precursor-B acute lymphoblastic leukemia (ALL) who experienced refractory thrombocytopenia and massive splenomegaly during standard induction chemotherapy. He was diagnosed with hemophatocytic lymphohistiocytosis (HLH) during induction. Clinical and laboratory evaluation showed no evidence of infectious cause to HLH. Pancytopenia and HLH persisted after consolidation therapy even with remission from leukemia. After failure to control HLH with ALL-directed therapy and HLH-directed therapy, the patient underwent unrelated donor hematopoietic stem cell transplantation 8 months after diagnosis. He is 34 months post-transplant and in remission from leukemia and HLH.     

Fatal Fournier's gangrene in a young adult with acute lymphoblastic leukemia

Fournier's gangrene (FG) is a fulminant necrotizing fasciitis of the external genitalia. Few reports of FG exist in patients with hematologic malignancies. We describe a case of fatal FG in a 21-year-old man with acute lymphoblastic leukemia who was receiving remission-induction chemotherapy. Despite early local surgery, administration of appropriate antibiotics, resurgery for wider debridement and aggressive ICU support he succumbed while pancytopenic to septic shock, 26 days after initiation of chemotherapy. Multi-drug resistant Pseudomonas aeruginosa was isolated from blood and scrotal cultures obtained at initial surgery. FG is a fulminant infection, especially in the face of profound cytopenias.     

Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens

OBJECTIVE: To determine the prevalence, duration, and a potential cause of humoral defect(s) in children with acute lymphoblastic leukemia (ALL) at least 1 year after completion of chemotherapy. STUDY DESIGN: Antibody titers for mumps, rubeola, rubella, tetanus and diphtheria toxoid, poliovirus serotypes 1, 2,and 3, Haemophilus influenzae type b, varicella, and hepatitis B were obtained from 100 children with ALL. Children with non-protective titers to these microbial antigens were re-vaccinated and re-studied after anamnestic vaccine challenge. RESULTS: The percent of children with ALL who had protective titers was markedly less than that anticipated for immunized control subjects. Longitudinally, many titers fluctuate between protective and non-protective antibody responses after re-immunization. The chemotherapy protocol used did not affect the ability of these children to express protective antibody responses. T-, B-, and NK-cell numbers and proliferative responses to mitogens were all normal. Age correlated with titer results for certain vaccines. CONCLUSIONS: Children in remission from ALL have a high prevalence of humoral immune defects that are not related to any specific chemotherapy regimen. This antibody deficiency may place children with ALL at risk for the development of these bacterial and viral diseases, even after completion of chemotherapy. Pediatricians, oncologists, or both should periodically monitor humoral immunity after chemotherapy and re-vaccinate these children, as needed, to ensure prolonged immunoprotection.     

Treatment and biology of pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80–90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g. age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease). Treatment for pediatric ALL typically consists of induction therapy with steroids, vincristine, and asparaginase with or without anthracycline, followed by multi‐agent consolidation including high‐dose methotrexate and re‐induction therapy. After consolidation, less intensive maintenance therapy is required for 1–2 years to maintain event‐free survival. Recently, using advanced genomic analysis technology, novel sentinel genomic alterations that may provide more precise stratification or therapeutic targets, were identified. Moreover, in the last decade germline variations have been recognized as similarly important contributors to understanding the etiology and sensitivity of ALL to treatment. A more individualized approach based on genomic features (somatic and germline) and treatment response, the introduction of newly developed agents such as molecular targeted drugs or immunotherapy, and social support including long‐term follow up are required for further improvement.     

儿童急性淋巴细胞白血病化疗相关严重不良反应的临床分析

目的 分析CCCG-ALL-2015方案治疗儿童急性淋巴细胞白血病（ALL）合并严重不良反应（SAE）的临床特点,探讨患儿发生SAE后死亡的危险因素。方法 回顾性分析2015年1月至2019年6月确诊并接受CCCG-ALL-2015方案化疗的734例ALL患儿化疗过程中发生SAE的临床特点,将发生SAE的ALL患儿分为死亡组（n=25）和存活组（n=31）,采用多因素logistic回归分析ALL患儿发生SAE后死亡的危险因素。结果 734例ALL患儿中,56例（7.6%）化疗后发生SAE（66例次）,高发于诱导缓解治疗阶段（41例次）。感染相关SAE发生46例次（70%）,包括脓毒性休克25例次（38%）,重症肺炎20例次（30%）,重症水痘1例次（2%）;感染相关SAE患儿中多数存在中性粒细胞缺乏（87%）。最常见的感染部位为血液系统和呼吸系统,最常见的病原微生物依次是革兰阴性菌、病毒、真菌和革兰阳性菌。出血相关SAE发生16例次（24%）,包括消化道出血11例次（17%）,肺出血4例次（6%）,颅内出血1例次（2%）。734例ALL患儿中死亡66例（9.0%）,25例患儿因SAE死亡,治疗相关病死率为3.4%,感染（72%）和出血（24%）是主要原因,合并重症肺炎是ALL患儿发生治疗相关死亡的独立危险因素（OR=4.087,95% CI：1.161~14.384,P=0.028）。结论 CCCG-ALL-2015方案治疗儿童ALL相关SAE主要发生于诱导缓解化疗阶段,感染相关SAE较多见。重症肺炎是ALL患儿发生治疗相关死亡的独立危险因素,需重视合并重症肺炎的治疗。     

Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low‐income countries: A proposal

Cure rates for children with acute lymphoblastic leukemia (ALL) are 80–85% in high‐income countries (HICs) in North America and Western Europe. However, cure rates are much lower in many low‐income countries (LICs), where most cases of ALL occur. Over the past several decades partnerships (“twinning”) between HIC and LIC pediatric oncology programs have led to major improvements in outcome for children with ALL in some LICs, often by developing time and resource intensive relationships that allow LIC centers to treat children with regimens similar or identical to those used in HICs. However, the resources are not available in most LICs to allow immediate introduction of intensive ALL treatment regimens similar to those used in HICs. With these thoughts in mind, we present a proposal for a systematic and graduated approach to ALL diagnosis, risk classification, and treatment in LICs. We have based the strategy and the proposed regimens on those developed by the Children's Cancer Group (CCG) and Children's Oncology Group (COG) over the past several decades, beginning with a first level regimen similar to CCG therapy of the early 1980s and then layering on successive treatment intensifications proven effective in randomized clinical trials. Simple monitoring rules are included to help centers decide when they are ready to add new treatment components. This proposal provides a framework that LIC centers can use to provide effective ALL therapy, particularly in regions of the world where few children are currently being cured. Pediatr Blood Cancer 2009;52:559–565. © 2009 Wiley‐Liss, Inc.     

Treatment for acute lymphoblastic leukemia in children is associated with papillary carcinoma of thyroid, but not with thyroid disfunction

AIM: The treatment of acute lymphoblastic leukemia (ALL) in children may cause sequelae, some appearing only at long-term follow-up. We investigated the thyroid gland morphology and the function of the pituitary-thyroid axis in a group of patients treated for ALL in childhood. METHODS: A cohort study was conducted at a tertiary medical center. Thirty-three children (22 males and 11 females; age: 11.9+/-3 years; range: 6 to 18 years) were studied. The mean age at the time of chemotherapy and prophylactic cranial irradiation (12-24 Gy) was 5.5+/-2.6 years (range: 1 to 14 years). The average length of the follow-up was 6.1+/-3 years (range: 2 to 12 years). Thyroid morphology (n=33) was evaluated by palpation and ultrasonography. Thyroid function (n=30) was evaluated measuring total T3 and T4, and by the thyrotrophin-releasing hormone (TRH) test. Prolactin secretion was assessed before and after injection of TRH to evaluate the diagnostic test accuracy. RESULTS: One out of the 33 children (3%) was found to have a papillary carcinoma of thyroid four years after ALL treatment. Thyroid function was normal in all the patients, however one case (3%) showed high TSH (9.2 microU/mL) and prolactin (37.5 ng/mL) basal levels, but normal responses to TRH (TSH = 17.8 microU/mL; prolactin = 82.3 ng/mL). These hormonal alteration were not confirmed at follow-up: TSH = 1.6 microU/mL and prolactin = 13.7 ng/mL. CONCLUSIONS: In this cohort of patients, the treatment of ALL was associated with one case of thyroid carcinoma, but it did not produce adverse effect on the thyroid function, at least after a follow-up lasted on average 6 years.     

细胞周期相关因子geminin在儿童急性淋巴细胞白血病中的表达

目的 研究细胞周期相关因子geminin蛋白及其mRNA在儿童急性淋巴细胞白血病中的表达.方法 以16例首次诊断且未治疗的急性淋巴细胞白血病患儿为实验组,16例正常儿童为对照组,采集其静脉血进行淋巴细胞分离,应用免疫组织化学染色法检测geminin蛋白在两组中的表达;用RT-PCR法检测gemininmRNA在两组中的表达.使用SPSS软件进行数据分析.结果 实验组geminin蛋白及geminin mRNA表达均高于对照组(P均<0.05);对照组geminin蛋白有表达,但其相应的mRNA不表达.结论 急性淋巴细胞性白血病细胞geminin过度表达,可能参与儿童急性淋巴细胞白血病的发生发展;正常淋巴细胞geminin存在蛋白与其相应的mRNA表达不一致的现象.     

bcr-abl-positive T-cell acute lymphoblastic leukemia associated with parvovirus B19 infection

The authors report an unusual presentation of a Philadelphia chromosome-positive acute lymphoblastic leukemia with two unusual features: a bcr-abl fusion mRNA coding for p210 protein and a T-cell immunophenotype. The patient was a 16-year-old boy who presented with septic shock and pancytopenia, likely precipitated by an acute parvovirus B19 infection. Management consisted of supportive therapy, followed by chemotherapy for T-cell acute lymphoblastic leukemia and stem cell transplantation. He died 8 months after transplant due to idiopathic pneumonia syndrome, but without evidence of relapsed disease.