Blastic transformation in chronic myelogenous leukemia: Experience with 50 patients

Fifty consecutive patients with blastic chronic myelogenous leukemia were evaluated clinically, morphologically, biochemically, and therapeutically. Forty-five patients had a preceding stable phase (38 Ph +, 7 Ph -); five patients presented with de novo Ph+ blast crisis. The most frequent clinical signs of impending blast crisis were weakness, fatigue, increasing splenomegaly, anemia, thrombocytopenia, marrow fibrosis, and a rising neutrophil alkaline phosphatase. Fever (unrelated to infection), skin infiltration, lymphadenopathy, hepatomegaly, thrombocytosis, and basophilia were much less common. The development of aneuploidy occurred in less than one-half of the total group. Myeloblastic morphology at blastic transformation was most frequent with occasional lymphoblastic, promyelocytic, and undifferentiated cases seen. Terminal deoxynucleotidyl transferase was present in one-third of the patients, but had no clear-cut relationship to the morphology. Response to treatment was generally disappointing (two complete and 15 partial remissions in 45 treated patients).     

Lymphoblastic conversion in chronic myelogenous leukemia.

A child presented with "acute leukemia" in which the blast cells resembled lymphoblasts and had negative cytochemical staining (PAS, Sudan black, and myeloperoxidase). Remission was induced and typical adult-type chronic myelogenous leukemia (CML) followed. Cytogenetic studies initially and during remission and subsequent "acute leukemia" relapses revealed the presence of the Philadelphia chromosome abnormality. Terminal transferase assay performed on peripheral blood blast cells was markedly elevated and soft agar culture growth parameters were typical of acute lymphoblastic leukemia T and B cell marker studies revealed no markers. This case report with supportive laboratory studies suggests that a cell line with lymphoid characteristics may predominate during acute leukemic transformation. This type of subclassification of leukemia may be of importance in therapeutic planning.     

Juvenile chronic myelogenous leukemia

Juvenile chronic myelogenous leukemia (JCML) is a malignant hematopoietic disorder of monocyte-histiocyte lineage that affects children less than 4 years of age. Since the disease represents only 2% of all childhood leukemias, experience with it has been limited even in large centers. This review summarizes our 10 year institutional study of JCML as well as a comprehensive literature survey. The goal of the article is to underscore the cardinal features of juvenile chronic myelogenous leukemia that are useful for diagnosis, and to highlight recent advances in the understanding of the biology and treatment of the disease.     

Allogeneic hematopoietic stem cell transplantation in pediatric chronic myelogenous leukemia cases: Hacettepe experience

Recently, there are emerging reports on the beneficial effect of imatinib mesylate for pediatric CML patients; however, the general recommendation is that high-risk CML patients with a human leukocyte antigen-identical donor should be transplanted within the first 12 months after diagnosis. Herein, the data of 16 allogeneic HSCT in 14 children with CML were analyzed retrospectively. In the present study, three-yr EFS was 54.1+/-10.8% and three-yr OS was found as 80.7+/-12.5%.     

小儿慢性粒细胞性白血病合并阴茎异常勃起一例

患儿男,11岁,住院号594203。因“阴茎异常勃起15h”于2004年5月3日凌晨零点八分急诊入院。患儿于入院前15h洗澡时无明显诱因出现阴茎勃起,勃起呈持续性,不能疲软,并感阴茎疼痛,可排尿,尿线较粗。在当地医院行镇静、冰盐水冷敷、冰盐水灌肠等处理不见好转,急来我院小儿外科就诊并收入院。患儿既往健康,但最近有乏力、消瘦的病史,无肝炎、结核等传染病史及接触史,无外伤及手术史,无药物食物过敏史。     

Allogeneic bone marrow transplantation in children with chronic myelogenous leukemia

PURPOSE: To determine the outcome of children undergoing allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) at the authors' institution. PATIENTS AND METHODS: Between 1985 and 1999, 18 allogeneic bone marrow transplantations were performed in 17 patients with CML at the Hospital for Sick Children in Toronto. Median age at diagnosis was 9.5 years (range 3-17). Fourteen patients had disease in the first chronic phase, one had disease in the second chronic phase, and two had disease in the accelerated phase. Preparative regimens varied, with radiation-based protocols used in eight patients. Thirteen donors were related (11 matched, 2 mismatched); four were unrelated (2 matched, 2 mismatched). Patients received T-cell-replete bone marrow a median of 7.5 months (range 2.2-22) from diagnosis. A median of 3.0 x 10(8)/kg nucleated cells was infused (range 1.6-6.7). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in 13 children. cyclosporine in three, and methotrexate in one. RESULTS: Primary graft failure occurred in one patient. Grade 2 acute GVHD or more developed in 11 of the 17 children (64%; grade 2 in 4, grade 3 in 7). Chronic GVHD occurred in 6 of the 16 patients at risk (37.5%; 5 extensive, 1 localized). No patient experienced overt or cytogenetic relapse. There were two deaths (12%): one from acute GVHD and cytomegalovirus pneumonia and the other from chronic GVHD. Probability of 5-year event-free survival was 87 +/- 9%. CONCLUSIONS: These results strongly support the practice of allotransplantation in children with CML, even in the setting of advanced disease and histoincompatibility. Efforts should be aimed at reducing the transplantation-related death rate.     

Congenital juvenile chronic myelogenous leukemia: Therapeutic trial with interferon alpha-2

A newborn with congenital juvenile chronic myelogenous leukemia (JCML) is described. The diagnosis was suggested by the characteristic clinical and hematologic presentation, and was confirmed by the results of in-vitro cultures of the hematopoietic progenitors, which showed excessive proliferation of monocytic colonies, with and without the addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF). Based on published in-vitro response of JCML cells to alpha interferon-2 (α IFN 2), we treated this child for 17 weeks with subcutaneous alpha interferon, 1,000,000 units per day. In contrast to previous in vitro results, treatment of this patient affected neither the clinical course of the disease, nor the in vitro growth of the peripheral blood-derived monocytic colonies. © 1993 Wiley-Liss, Inc.     

Adult form of chronic myelogenous leukemia in childhood--a retrospective analysis of 20 patients

The initial findings and the course of 20 children and adolescents with adult CML from 10 children hospitals were analyzed retrospectively. The Philadelphia chromosome was found in 18 patients. Initial findings, the course and the prognosis were similar to those published from adult patients. 7 of the 11 children who received chemotherapy alone are still alive with a median survival time of 26 months (range: 14 to 68 months). One patient survived the third blast crisis. For 9 children with a bone marrow transplantation during the chronic phase (median time before transplantation 30 months) the follow-up of 7 months is still too short. 4 of these patients died following graft versus host reaction, 5 show no signs of a renewed occurrence of CML so far. Since CML is rare in children, there is little large scale experience. Hence, there is an urgent need for the prospective and cooperative study of these patients.     

Philadelphia chromosome-positive chronic myelogenous leukemia following apparent acute lymphoblastic leukemia

The observation that Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) may progress to chronic myelogenous leukemia (CML) has been well-documented among adult patients but reported only rarely in children. In this report, we describe a pediatric patient with atypical ALL, who subsequently went on to develop classical adult-type CML. This patient is unique and important because of the unusual clinical findings that she exhibited during the "ALL" phase, namely, extreme thrombocytosis, marrow fibrosis, and persistent splenomegaly, which heralded the onset of frank CML. It is suggested that the patient with presumed, but atypical, ALL be carefully evaluated for CML presenting in lymphoblastoid crisis, and that all patients with the morphologic diagnosis of ALL undergo complete cytogenetic and immunologic marker studies to confirm the diagnosis.     

Juvenile chronic myelogenous leukemia: differentiation from infantile cytomegalovirus infection

Differentiation between cytomegalovirus (CMV)-associated disease and juvenile chronic myelogenous leukemia (JCML) in infants excreting CMV may be difficult. It is important to make a prompt, definitive diagnosis since the management differs. A 3-month-old infant presented with clinical findings that mimicked both disorders and a plan was developed to make the correct diagnosis. Clonogenic assays and liquid cultures of patients' peripheral blood and bone marrow showed findings that are recognized as the hallmark of JCML, namely, impaired growth of normal hematopoietic progenitors, and excessive, autonomous proliferation of monocyte/macrophage elements. The urine was positive for CMV, and there was a significant rise in the anti-CMV antibody titer over 4 weeks, indicating a postnatal CMV infection. Despite this, freshly obtained and cultured marrow cells as well as a liver biopsy were negative for CMV by immunoassay, by anti-CMV monoclonal antibody testing, and by electron microscopy. Because of these results, the diagnosis of CMV infection was established but could not account for all of the abnormal clinical and hematological findings. Thus, the diagnosis of JCML was also substantiated and antileukemic therapy was initiated with confidence.     

Osteolytic lesion in chronic myelogenous leukemia (CML)

Report of a 13-year-old boy who developed osteolytic lesions in the chronic phase of myelogenous leukemia. Five months later a blastic crisis followed.     

Juvenile chronic myelogenous leukemia and dermal histiocytosis. In Von Recklinghausen's disease.

A 4-year-old boy with multiple café-au-lait spots and a family history of neurofibromatosis had generalized edema, histiocytic rash characterized by benign histiocytic infiltration, hepatomegaly, and life-threatening infection. Six months later, progessive splenomegaly led to juvenile chronic myelocytic leukemia that eventually proved fata. The case represents an important association of diseases.     

Juvenile chronic myelocytic leukemia: experience with intensive combination chemotherapy

Six children with juvenile chronic myelocytic leukemia (JCML) with adverse prognostic features were treated with intensive combination chemotherapy similar to that utilized in patients with acute nonlymphocytic leukemia (ANLL). Despite obtaining hematologic remissions after induction therapy, clinical findings of extramedullary disease persisted. The use of intensive post-induction chemotherapy did not erradicate persistent extramedullary disease, and all patients developed hematologic relapse and progressive disease at a median of 8 months. The median survival of the treated patients was 15 months. The use of intensive ANLL therapy in poor prognosis JCML does not improve the survival rates reported with less intensive regimens but does have value in producing hematologic remissions that may be useful in preparing patients for bone marrow transplant.     

Cytomegalovirus sinusitis in a child with chronic myelogenous leukemia following bone marrow transplantation

Cytomegalovirus (CMV) is a common opportunistic pathogen. CMV sinusitis has been described in acquired immunodeficiency syndrome (AIDS) patients, but not in other immune compromising conditions. In this report, we describe CMV sinusitis in a child with chronic myelogenous leukemia (CML) following bone marrow transplantation.     

Acute transformation of chronic lymphocytic leukemia

A patient with chronic lymphocytic leukemia had typical cell morphology and a characteristic clinical course for 7 years. He then developed progressive disease with a rapidly rising WBC which proved resistant to chemotherapy. The cells resembled lymphoblasts. Immunoperoxidase studies demonstrated identical immunoglobulin light and heavy chains on the surface of both mature lymphocytes and lymphoblasts. Using a recently described monoclonal antibody, B5, a "blast" antigen was demonstrated on the lymphoblast cell surface, but not on the mature lymphocytes. On the basis of morphological and immunological studies, we suggest that the patient's malignant clone transformed from chronic lymphocytic leukemia to acute lymphoblastic leukemia.     

Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of oncogenic KRAS

Previous studies have reported several cases of juvenile myelomonocytic leukemia (JMML) developing blastic transformation during an indolent clinical course, but the underlying mechanism of transformation is still not well understood. In this report, we describe a case of JMML with blastic transformation possibly caused by additional copy number gains of the KRAS mutant allele. We have discovered that the copy number gain of the mutant allele is an additional possible cause of blastic transformation in JMML.     

Successful treatment of invasive aspergillosis in two patients with acute myelogenous leukemia

Invasive aspergillosis is a severe, devastating fungal infection that is seen in patients with hematologic malignancies and profound neutropenia. Despite aggressive treatment, the outcome is poor without neutrophil recovery. The authors describe two children with acute myelogenous leukemia (AML) with extensive invasive aspergillosis who were successfully treated both for their infection and the underlying malignancy. These patients were treated aggressively for their infections and simultaneously were able to complete treatment of their AML. Currently both patients are alive without evidence of fungal infection or AML. Patients with hematologic malignancies can survive severe, invasive aspergillosis during prolonged periods of neutropenia with a combination of antifungal and growth factor therapies, donor granulocyte infusions, and surgical debridement.