Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia

 Therapy for childhood acute lymphoblastic leukemia (ALL) is entering a new era in terms of quality-of-life. In the current study, 21 patients with childhood-onset ALL were assessed for linear growth, bone mineral density (BMD), and endocrinological status, focusing especially on longitudinal analysis of the growth of each patient. Linear growth was uniformly attenuated during therapy in all patients. In contrast, after the cessation of therapy, the growth of each patient varied widely from attenuated to dramatic catch-up growth. In pubertal survivors who had received chemotherapy and cranial irradiation during prepuberty, the degree of growth after the cessation of therapy was negatively correlated with changes in height Z scores during therapy (r = −0.76, P = 0.004). One of the factors involved in catch-up growth, urinary N-telopeptide/creatinine (U-NTx/Cr), was significantly higher in patients whose Z scores decreased after cessation of therapy (P = 0.01), despite normal pubertal development and normal endocrinological assessments. The present study revealed individual differences in linear growth after the cessation of therapy and suggests the importance of catch-up growth during puberty. Received: August 29, 2002 / Accepted: November 11, 2002 Acknowledgments. This study was supported by grants from the Ministry of Health and Welfare and the Ministry of Education of Japan. Offprint requests to: H. Tanaka     

Pancreatic pseudocyst complicating treatment of acute lymphoblastic leukemia

In the management of children with acute lymphoblastic leukemia, L-asparaginase has become established as an effective drug in the usual multi-agent therapy; and the significance of pancreatitis as a complication of this drug is well recognized. Less well appreciated, however, is the progression of such pancreatitis in some patients to pseudocyst formation and the possible necessity for surgical management. Two adolescent girls who developed pancreatic pseudocysts while being treated with L-asparaginase are described in this report. Both were being treated for acute lymphoblastic leukemia for periods of 18 and 4 months, respectively, prior to the onset of pancreatitis. Both were in remission of their leukemic disease when typical clinical and laboratory manifestations of acute pancreatitis developed. In one girl, a pancreatic pseudocyst became apparent 2 weeks following the diagnosis of acute pancreatitis and in the other girl, this complication developed over a period of 8 weeks. The usual nonsurgical management of pancreatitis over protracted periods of time was ineffective in the treatment of the pseudocysts. Surgical drainage (internal in one and external in the other) was successful in both in eradicating the pseudocyst, and in neither did further evidence of pancreatic disease subsequently occur. In both resumption of chemotherapy, omitting L-asparaginase, was well tolerated. One has been in remission of leukemia and in good health for a 3-year period of follow-up observation, while the other subsequently had a relapse of leukemia and died 18 months following the onset of pancreatitis.     

Impact on relapse of corticosteroid therapy after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

Imahashi N, Inamoto Y, Seto A, Watanabe K, Nishiwaki S, Yanagisawa M, Shinba M, Yasuda T, Kuwatsuka Y, Atsuta Y, Kodera Y, Miyamura K. Impact on relapse of corticosteroid therapy after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.
Clin Transplant 2010: 24: 772–777. © 2009 John Wiley & Sons A/S. Abstract: Corticosteroids are often used following allogeneic hematopoietic stem cell transplantation (HSCT) to control complications such as graft‐versus‐host disease (GVHD). However, there is some concern that corticosteroids may suppress the graft‐versus‐leukemia effect and increase leukemia relapse. To evaluate the effect of corticosteroids on relapse, we analyzed 112 adult patients who received their first allogeneic HSCT for acute myeloid leukemia at our institution between 1997 and 2007. Fifty‐seven patients (50.9%) received corticosteroid therapy. Patients who had corticosteroid therapy included higher proportion of patients who developed GVHD. In multivariate analysis, with corticosteroid administration entered as a time‐dependent covariate, corticosteroid administration was not a risk factor for relapse (p = 1.00, hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.53–1.88), but it was associated with higher non‐relapse mortality (NRM) (p < 0.001, HR 55.5, 95% CI 7.42–416) and lower overall survival (p < 0.001, HR 2.68, 95% CI 1.56–4.61). The higher NRM associated with corticosteroid administration was mainly due to the increased deaths caused by the complications themselves, which required corticosteroid therapy. The findings of this study indicate the importance of controlling complications after allogeneic HSCT. The strategy of refraining from indispensable corticosteroid therapy because of the excessive concerns about relapse should be avoided.     

Male fertility in long-term survivors of childhood acute lymphoblastic leukaemia

To study long-term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1-16.3 years) and the subsequent assessment (median 18.6 years; range 15.4-26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis. All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal greater than or equal to 15 mls) and a raised basal FSH level (13 UI 1-1; normal less than or equal to 6 IU 1-1). All six men with germ-cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen. Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age-matched normal = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)     

On a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia

The Authors describe the case of a 14-year-old girl who developed a multifocal osteonecrosis (ON), after treatment with chemotherapy and corticosteroids for acute lymphoblastic leukemia (ALL). She came to our attention about 6 months after the beginning of treatment complaining of pain in her left knee and later in both hips and shoulders. Radiography and MRI confirmed the presence of avascular ON at all these sites. The patient underwent bilateral total hip arthroplasty, which was still functioning well at the last follow-up visits at 5 years, and at 5 years and 4 months. ON is increasingly recognized as a complication of the treatment of cancer in children and adolescents, and as patients now frequently survive ALL into adulthood, orthopedists will be increasingly called on to manage this complication affecting multiple joints in children and young adults.     

Role of hematopoietic cell transplantation in relapsed acute promyelocytic leukemia

The use of all trans-retinoic acid and arsenic trioxide combination as the induction regimen for acute promyelocytic leukemia (APL) has revolutionized the management and outcomes of this disease. Modern risk-adapted frontline therapy has provided excellent therapeutic results. However, significant numbers of APL patients relapse after frontline therapy, and the optimal management strategy for relapsed APL, specifically the role and type of hematopoietic cell transplantation (HCT) are still to be defined. Both autologous and allogeneic HCTs are associated with durable remission and prolonged survival when utilized in appropriate disease settings. Once remission has been achieved, consolidation with autologous HCT for APL patients with negative minimal residual disease (MRD) status, and with allogeneic HCT for APL patients with positive MRD status appear to offer the best long-term outcomes. In this article, we provide a comprehensive review of existing literature on the efficacy of HCT in treatment of relapse/refractory APL and we discuss the appropriate use of this modality.     

Osteonecrosis of the talus of a child with acute lymphoblastic leukemia: A case report

Osteonecrosis (ON) is a disabling complication of acute lymphoblastic leukemia (ALL) treatment in children and young adults. Isolated talus involvement is thought to be uncommon. A unique case of a 11-year-old female patient with ON in her left talus which developed six months after the completion of chemotherapy that she received for ALL is reported. A conservative treatment protocol was followed including activity modification, analgesia and prevention of weight-bearing. However, the disease significantly progressed during follow-up period. The present study makes an important contribution to the literature with unusual involvement pattern and location of ON after ALL treatment and with a long follow-up duration.Level of evidenceIV.     

Renal function during and after treatment for acute lymphoblastic leukemia in children

Renal function tests (cystatin C, serum and urine creatinine, creatinine clearance, serum and urine ₂-microglobulin, microalbuminuria, osmolality) were performed in 21 children at the diagnosis and during the treatment for acute lymphoblastic leukemia (ALL) (group I) and in 37 children (group II) treated for ALL 3.9±3.7 years before the study. The results were compared to 20 healthy children. Mean values of renal tests were in normal range at all points of analysis in groups I and II compared to the control group. Transitory higher cystatin C values (but in normal range) were observed after methotrexate administration and after the end of treatment. Deteriorated renal function was observed in one child during the treatment (after each protocol) and in five children treated previously for ALL. In conclusion, combined treatment for ALL is not associated with severe or long-term impairment of renal function.     

Poorly differentiated sarcoma of the prostate causing obstructive acute renal failure: A case report

A 12-year-old boy presented to the Naha Municipal Hospital complaining of back pain. After intravenous pyelography, computed tomography, magnetic resonance imaging, ultrasonography and biopsy, he was suspected to have sarcoma of the prostate and was referred to the University of the Ryukyus Hospital. Acute renal failure of the post renal type was evident, accompanied by minimal hydronephrosis. Emergency hemodialysis and right ureterostomy were performed, as was a transurethral prostate biopsy. The specimen showed a poorly differentiated sarcoma not otherwise classifiable. After recovery from surgery, chemotherapy was attempted over 2 months, but the patient died of tumor 250 days after admission.     

Precursor B-cell lymphoblastic leukemia as a cause of a bilateral nephromegaly

Nephromegaly and non-oliguric acute renal failure is an unusual manifestation of lymphoblastic infiltration of the kidneys. We report the clinical history of a female child where a precursor B-cell lymphoblastic proliferation was diagnosed at the age of 21 months by a surgical renal biopsy for an unexplained bilateral nephromegaly. Lymphoblastic infiltration should be suspected in any patient presenting with unexplained renal failure and enlarged kidneys. The importance of renal biopsy to identify the etiology of renal failure and nephromegaly is emphasized.     

Simultaneous occurrence of atypical hemolytic uremic syndrome and acute lymphoblastic leukemia: a case report and literature review

A 3.5-year-old girl with fever had a pancytopenic blood smear that also showed schistocytes and blast cells. Bone marrow examination resulted in a diagnosis of acute lymphoblastic leukemia (ALL). Although creatinine on admission was normal, she had mild hematuria and moderate proteinuria. Chemotherapy was started, but she was initially given only steroids (dexamethasone) due to high liver enzymes. Her renal parameters worsened, and her creatinine doubled. She also developed nephrotic-range proteinuria and hypertension. Renal biopsy showed thrombotic microangiopathy that was clinically consistent with hemolytic uremic syndrome (HUS). Some reports of HUS preceding ALL do exist. However, to the best of our knowledge, this is the first case that describes ALL and HUS presenting simultaneously.     

急性淋巴细胞白血病患儿父母养育倦怠现状及影响因素

目的 探讨急性淋巴细胞白血病患儿父母养育倦怠现状及影响因素,为临床针对性护理干预提供参考。方法 采用一般资料问卷、养育倦怠评估量表、疾病不确定感量表和领悟社会支持量表对广州市4所三级甲等医院收治的259例急性淋巴细胞白血病患儿的父母进行调查。结果 患儿父母养育倦怠得分为（90.19±14.25）分;患儿疾病严重程度、与患儿关系、家庭人均月收入、疾病不确定感总分、领悟社会支持总分是养育倦怠的主要影响因素（均P<0.05）,可解释总变异的50.9%。结论 急性淋巴细胞白血病患儿父母存在养育倦怠,给予患儿疾病严重程度高、患儿母亲、家庭人均月收入低的患儿父母更多关注,降低其疾病不确定感并提高其领悟社会支持水平,从而降低其养育倦怠水平。     

Assessment of serum prostate specific antigen in childhood

OBJECTIVE: To investigate serum prostate specific antigen (PSA) levels with age and sex in childhood. SUBJECTS AND METHODS: This prospective study included 205 children (123 boys, 82 girls; mean age 59.27 months, sd 3.78, range 2 days to 204 months) with no urogenital or endocrine disorders. PSA levels were measured using a highly sensitive, "third-generation" PSA (time-resolved immunofluorometric) assay, able to detect PSA levels of > or = 1 ng/L (0.001 ng/mL). Children were divided into four groups by age, i.e. A (0-12 months; 34 boys/20 girls); B (13-48, 37/21); C (49-144, 41/32); and D (> 144, 11/9). The data were analysed statistically using analysis of variance. RESULTS: An accurate measurement of PSA was possible in both sexes using the assay. The median (sd, range) PSA level in boys was 38.41 (1.318, 1-2768) ng/L, and in girls 4.059 (1.392, 1-287) ng/L. There were no significant differences between girls at all age groups, or between the sexes for groups A-C, but levels were significantly higher in boys in group D (30 times that in girls), at 142.59 (1.53) and 4.85 (1.58) ng/L (P < 0.01). CONCLUSIONS: PSA levels do not differ significantly between boys and girls until 12 years old, after which there is a significant and steep increase in PSA in boys, reflecting the development of the prostate. Assessing PSA in children could be used as a potential marker in the diagnosis and follow-up of urogenital disorders.     

Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study

A total of 123 consecutive patients with advanced‐stage, acute leukemia undergoing HSCT from HLA‐identical sibling donors were analyzed. A G‐CSF‐primed DLI was planned within day 60 post‐transplantation before hematologic relapse was diagnosed. Fifty of the 123 individuals received prophylactic DLI, and 73 individuals received no prophylactic treatment. The incidence of grades II–IV acute graft‐versus‐host disease (GVHD) was 17% for patients receiving DLI and 23% for patients not receiving DLI (p = 0.35). The incidence of chronic GVHD was 38% for patients receiving DLI and 17% for patients not receiving DLI (p = 0.021). The two‐yr cumulative incidence of relapse was significantly lower in patients who received prophylactic DLI (46%) compared with patients who did not receive prophylactic DLI (66%) (p = 0.02). The three‐yr probability of overall survival was higher in patients who received prophylactic DLI (36%) than in patients who did not receive prophylactic DLI (11%) (p = 0.001). The leukemia‐free survival was also higher in patients who received prophylactic DLI (29%) than in patients who did not receive prophylactic DLI (9%) (p = 0.001). Our comparisons suggest that the prophylactic use of DLI can significantly increase survival of patients with advanced‐stage, acute leukemia who receive HLA‐identical sibling HSCT.     

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy

OBJECTIVE: To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. PATIENTS AND METHODS: Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. RESULTS: In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. CONCLUSIONS: Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.     

Neutropenic enterocolitis as a presenting complication of acute lymphoblastic leukemia: an unusual case marked by delayed perforation of the descending colon

Neutropenic enterocolitis (NE) is a life-threatening complication most commonly seen in patients receiving intensive chemotherapy for acute leukemia. The condition usually affects the terminal ileum, cecum, or ascending colon. In rare instances, NE may occur before the initiation of chemotherapy or involve more distal bowel. The authors report the case of a 2-year-old girl who had NE affecting the descending colon as a presenting complication of acute lymphoblastic leukemia. Despite aggressive medical interventions, including granulocyte infusions, she had a delayed bowel perforation that was managed successfully with surgery. This case highlights the challenges of treating patients who have NE as an initial manifestation of acute leukemia.     

Acute lymphoblastic leukemia in a child with nephrotic syndrome

A 5-year-old African-American male was diagnosed with nephrotic syndrome (NS). Because of concomitant leukopenia, bone marrow aspiration was performed, which did not demonstrate a hematological malignancy. The patient received standard daily steroid therapy for treatment of NS. Steroid resistance at 5 weeks of therapy led to a renal biopsy, which documented focal segmental glomerulosclerosis (FSGS). He was begun on cyclosporin A (CsA) and later switched to tacrolimus because of side-effects of CsA. Seven months after the initial diagnosis of NS, the patient was diagnosed with acute lymphoblastic leukemia (ALL). The patient is in complete remission of ALL and partial remission of NS with continued nephrotic-range proteinuria. Review of the literature shows four other cases of pediatric ALL after NS. No particular immunosuppressive agent seemed to be causative in the evolution of ALL. Although the exact mechanism for development of ALL after NS is unknown, the incidence of leukemia may be increased after immunosuppressive therapy when used in this context.     

急性白血病骨髓MRI诊断价值

目的 探讨MRI对急性白血病的诊断价值。方法 选择经临床确诊为急性白血病但未经治疗患者21例、化疗缓解组16例,对照组30例,进行腰骶椎和骨盆等部位的MRI检查。分析急性白血病治疗前后骨髓的MRI表现。结果 急性白血病治疗前组21例,骨髓T1信号降低,T2信号变化不明显。化疗缓解组16例表现为T1信号不同程度的增高。结论 急性白血病骨髓MRI具有一定的特征性,对估计病情、评价疗效及避免多次重复骨穿等有一定意义。     

A-I型前列腺穿刺器活检筛选前列腺癌的临床意义

目的验证A-I型前列腺穿刺器对临床上前列腺特异性抗原(PSA)>4ng/ml和(或)前列腺直肠指诊、B超发现结节者进行前列腺癌筛查的临床意义。方法采用A-I型前列腺穿刺器,对36例PSA>4ng/ml或有前列腺结节者,在食指引导下进行前列腺左右叶的尖、中间、尾部和触及结节处活检。结果有结节者17例中发现前列腺癌(PCA)5例(29.4%);PSA>4.0ng/ml的34例中,PCA检出15例(44.12%)。分析显示:A-I型前列腺穿刺器与B-超引导系统相比较,对血清PSA>4.0ng/ml者的PCA检出率有明显的差异(x2=5.568,　P<0.05)。结论A-I型前列腺穿刺器完全可以满足临床对筛查前列腺癌的要求,是一种操作简便、易用、费用低廉的前列腺疾病的诊断器械,值得临床推广。