Chikako Tono

Distinct Impact of Imatinib on Growth at Prepubertal and Pubertal Ages of Children with Chronic Myeloid Leukemia

OBJECTIVE To determine the extent of growth impairment resulting from imatinib treatment in children with chronic myeloid leukemia (CML). STUDY DESIGN Clinical records of 48 chronic-phase CML children administered imatinib as the first-line therapy between 2001 and 2006 were analyzed retrospectively. Cumulative change in height was assessed using the height height-SDS and converted height data from age- and sex-adjusted Japanese norms. RESULTS A decrease in height-SDS was observed in 72.9% of children, with a median maximum reduction in height-SDS of 0.61 during imatinib treatment. Median follow-up time was 34 months (range, 10-88 months). Growth impairment was seen predominantly in children who started imatinib at a prepubertal age compared with those who started at pubertal age. Growth velocity tended to recuperate in prepubertal children with growth impairment, as they reached pubertal age, suggesting that imatinib had little impact on growth during puberty. CONCLUSIONS Growth impairment was a major adverse effect of long-term imatinib treatment in children with CML. We report the distinct inhibitory effect of imatinib on growth in prepubertal and pubertal children with CML. We should be aware of growth deceleration in children, especially in young children given imatinib before puberty and subjected to prolonged exposure.

Outcome of 125 Children with Chronic Myelogenous Leukemia Who Received Transplants from Unrelated Donors: The Japan Marrow Donor Program

Because of a small number of patients, only a few studies have addressed the outcome of bone marrow transplantation (BMT) in children with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), who receive graft from a volunteer-unrelated donor (VUD), especially after practical application of imatinib mesylate. The outcomes of BMT from a VUD in 125 children with Ph+ CML were retrospectively reviewed. Patients were identified through the Japan Marrow Donor Program as having undergone BMT between 1993 and 2005 and were aged 1-19 years at the time of transplant (median age, 14 years). The probabilities of 5-year overall survival (OS) and leukemia-free survival (LFS) were 59.3% and 55.5%, respectively. Multivariate analysis identified the following unfavorable survival factors: infused total nucleated cell dose<314 x 10(6) /kg (relative risk [RR]=2.43; 95% confidence interval [CI]=1.33-4.44; P=.004), advanced phase (RR=2.43; 95% CI=1.37-4.31; P=.004), and no major cytogenetic response (MCyR) at the time of BMT (RR=6.55; 95% CI=1.98-21.6; P=.002). Of the 17 patients treated with imatinib, 15 (88%) achieved MCyR at the time of BMT, and this group had an excellent 5-year OS of 81.9%. Disease phase, infused total nucleated cell dose, and cytogenetic response were independent risk factors for survival of unrelated BMT. These findings provide important information for assessing the indications for and improving outcome in unrelated BMT for the treatment of pediatric CML.

Successful umbilical cord blood transplantation for intractable eczematous eruption in hypohidrotic ectodermal dysplasia with immunodeficiency.

Anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID) is an X-linked recessive genodermatosis, characterized by a severe eczematous eruption, hypohidrosis, dental anomalies, alopecia and immunodeficiency. We report a case of intractable eczematous eruption in a patient with EDA-ID, which disappeared completely after allogenic transplantation of umbilical-cord blood. A 4-month-old Japanese boy with a pruritic eruption over his whole body since birth was referred to our clinic. On physical examination, diffuse erythema and reddish papules were seen, with evidence of scratching over most of the body, which was compatible with atopic dermatitis (Fig. 1). In addition, dry skin with flaky scales was found on the chest, back and limbs. Histological examination of a skin biopsy specimen found spongiotic changes in the epidermis and perivascular lymphoid and eosinophilic infiltration in the superficial dermis. Laboratory investigations deficient cellular immunity.

Leukostasis in Children and Adolescents with Chronic Myeloid Leukemia: Japanese Pediatric Leukemia/Lymphoma Study Group

The details of leukostasis in children and adolescents with chronic myeloid leukemia (CML) are unknown. This study determined the characteristics of leukostasis in children and adolescents with CML.

Successful Outcome of Mismatched Hematopoietic Stem Cell Transplantation from a Related Donor in an Infant with Acute Lymphoblastic Leukemia and 9 ; 11 Translocation : Case Report and Review of the Literature

Although infants with acute lymphoblastic leukemia (ALL) and MLL gene rearrangements have a poor prognosis, those with acute myeloid leukemia (AML) have been shown to have a superior outcome with intensive chemotherapy alone despite the presence of MLL gene rearrangements. We report the case of an ALL infant with t(9;ll), a common cytogenetic abnormality in infant AML, who after relapse underwent successful hematopoietic stem cell transplantation (HSCT) from her HLA 2-loci-mismatched mother. Analysis of the outcome among ALL infants with MLL gene rearrangements registered in the Japan Infant Leukemia Study between 1996 and 1999 showed the event-free survival of patients with t(9;11) was not different from that of those with other 11q23 translocations. Most of the patients with t(9;11) described in the reviewed literature also experienced either induction failure or early relapse after achievement of complete remission, but some of them were rescued with subsequent HSCT. These findings suggest that infant ALL with t(9;11) has features distinct from those of infant AML with the same karyotype and that the prognosis among these patients can be improved only with the combination of intensive chemotherapy and HSCT. An appropriate strategy for the treatment of ALL infants with different 11q23 translocations must be clarified.

Sporadic case of hemoglobin Bushwick detected by chance in aplastic crisis.

causes of congenital non-spherocytic hemolytic anemia, with over 90 molecular variants of it having been reported so far in the world.1 The US-Hb precipitates within red blood cells (RBC) as insoluble inclusions or Heinz bodies, because of an important abnormality in the primary structure of the globin chain. However, the clinical manifestations of US-Hb are variable and range from chronic hemolytic anemia, which is nearly asymptomatic, to life-threatening severe hemolysis. Human parvovirus (HPV) B19 is known to cause erythema infectiosum and has also been well known to trigger aplastic crisis in patients with chronic hemolytic anemia.2 Sometimes it may cause the first episode of anemia in patients with previously undetected US-Hb and has led to their diagnosis. We experienced a sporadic case of hemoglobin (Hb) Bushwick, a case that resulted from sporadic mutation and presented clinically with aplastic crisis due to HPV B19 infection.

Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group

The details of the sequential use of imatinib for first‐line treatment followed by second‐generation tyrosine kinase inhibitors (2G‐TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G‐TKIs following imatinib in pediatric chronic phase (CP)‐CML.

Flow cytometric analysis as an additional predictive tool of treatment response in children with chronic-phase chronic myeloid leukemia treated with imatinib

Bone marrow samples of newly diagnosed children with chronic‐phase chronic myeloid leukemia (CML) were obtained at diagnosis and after imatinib initiation and stained with anti‐human CD34, CD38, CD123, CD45RA, cMpl, and lineage antibodies. Flow cytometric analysis revealed that granulocyte macrophage progenitor predominance in CML progenitors at diagnosis and elevated cMpl expression in bone marrow progenitors at 3 months may predict poor outcome in children with chronic‐phase CML treated with imatinib. We recommend flow cytometric analysis of bone marrow in the early phase of treatment, as it is a convenient tool that may predict treatment response and guide CML management.