Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.     

Hypoplastic leukemia successfully treated with low-dose aclarubicin: a case report

Low-dose aclarubicin (LDACR) therapy is one of the differentiation induction therapy, such as low-dose cytosine arabinoside therapy, 1 alpha, 25 dihydroxy-vitamin D3 or retinoic acid therapy, for myelodysplastic syndrome and atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this LDACR therapy. On admission, she was suffered from general fatigue and her peripheral blood smear showed pancytopenia with 23% of myeloblasts. Bone marrow examination revealed a moderately hypoplastic marrow with 35.4% of myeloblasts. She was diagnosed as having hypoplastic acute myelogenous leukemia. Thereafter, 20 mg of aclarubicin was given daily by one-shot intravenous injection for 10 days. After this LDACR therapy, myeloblasts disappeared from her peripheral blood and pancytopenia improved. Bone marrow examination showed increase in nuclear cell counts and she achieved complete remission. In this article, we report the clinical course of this patient and discuss the effect of LDACR therapy as useful chemotherapy for this patient.     

Acute megakaryocytic leukemia presenting as hypercalcemia with skeletal lytic lesions

Acute megakaryocytic leukemia (AML M7) is a rare type of acute myelogenous leukemia in adults, commonly presenting with myelofibrosis. This report describes a case of a 32-yr-old male who presented with hypercalcemia and bony lytic lesions, in the absence of myelofibrosis. The diagnosis of AML M7 should be considered in a patient with pancytopenia, lytic lesions and hypercalcemia.     

Chronic myelogenous leukemia and Sweet syndrome

We report a 64-year-old woman with chronic myelogenous leukemia of 3 years duration who developed Sweet syndrome. Improvement in her blood counts after hydroxyurea was not associated with a decrease in size of the skin lesions. However, the cutaneous lesions of Sweet syndrome quickly resolved with systemic prednisone. Sweet syndrome has only been documented in the literature for five other chronic myelogenous leukemia patients. The characteristics, treatment, and differential diagnosis of this disorder in chronic myelogenous leukemia patients are reviewed.     

Transformation of refractory anemia with excess of blasts into acute myelogenous leukemia with Ph-negative chronic myelogenous leukemia-like characteristics

We report a 56 year old patient with acute myelogenous leukemia (FAB classification: M2), in whom the number of mature myeloid cells similar to those seen in Ph-negative chronic myelogenous leukemia increased markedly 2 months after the diagnosis of refractory anemia with excess of blasts (RAEB). This is a rare case of leukemic evolution as a terminal event of RAEB.     

Chronic neutrophilic leukemia

Summary Chronic neutrophilic leukemia (CNL) is a very rare entity, which has to be included among the chronic myeloid leukemias. Once an underlying cause of neutrophilia is excluded, the diagnosis of CNL is based on exclusion of chronic granulocytic and other types of chronic myeloid leukemias. The classification proposed by Sheperd et al. has proven to be helpful, but it must be completed by cytogenetic analysis and the search for bcr rearrangement by molecular biology methods, in order to confirm the absence of Philadelphia chromosome and of bcr-abl hybrid gene. We report here four cases of CNL, with confirmed absence of bcr rearrangement in two cases. Two patients died, 12 and 8 years after diagnosis, the second one following transformation into myelofibrosis with myeloid metaplasia. The other two died of acute myelogenous leukemia, the first one, 25 years after diagnosis of CNL, following a 3-year phase of acceleration. The last patient presented combined features of CNL and refractory anemia with excess of blasts, and was characterized by both progressive leukocytosis and severe thrombocytopenia; acute transformation into acute myelogenous leukemia occurred 6 months after diagnosis and death 1 month later. Among the 30 cases reported so far, plus the four presented here, combined myelodysplastic features were observed in five cases and transformation into acute myelogenous leukemia in six. Chronic neutrophilic leukemias should be reported regularity, in view of the uncertain and low frequency of this hematological disease.     

Busulfan-induced sideroblastic anemia

Patients in the stable phase of chronic myelogenous leukemia (CML) are usually treated with busulfan. The bone marrow of patients with CML may be exquisitely sensitive to busulfan, and occasionally such patients develop pancytopenia, secondary to hypoplasia or aplasia of the bone marrow, which is presumed to be due to busulfan-induced marrow toxicity. We report a case of Philadelphia chromosome-positive CML who developed pancytopenia while being treated with busulfan; however, the patient's bone marrow was not hypoplastic or aplastic but rather hyperplastic with sideroblastic changes. Busulfan is not known to cause sideroblastic changes, so this was considered to herald a transformation into acute leukemia. Busulfan was stopped, and only supportive treatment was given. To our surprise approximately 22 weeks after busulfan was stopped, the sideroblastic changes had disappeared and the bone marrow again showed features of CML. This case suggests that busulfan may cause sideroblastic anemia.     

Emergence and decrement of Ph-negative clone with trisomy 8 in CML during imatinib therapy

An increase in the presence of the Ph-negative, trisomy 8 clone has been reported in chronic myelogenous leukemia (CML) under imatinib therapy, but any impact of the clone on patient prognosis remains uncertain. We report here on a 42-year-old male with CML who received imatinib after failure of interferon-alpha therapy. A chromosomal analysis revealed 18/20 trisomy 8 in bone marrow at 10 months of imatinib administration. Continuing imatinib at 300 mg daily resulted in a decrease in the number of trisomy 8 clones as well as the disappearance of Ph clone. Furthermore, the patient's pancytopenia was gradually improved. Imatinib therapy could be continued even with the emergence of trisomy 8.     

Sweet's syndrome and accelerated phase of chronic myelogenous leukemia

 Sweet's syndrome is a neutrophilic dermatosis characterized clinically by raised, erythematous, tender lesions on the face, neck, upper thorax and extremities. Several diseases have been associated with this entity. We report a case of Sweet's syndrome associated with chronic myelogenous leukemia: a 48-year-old woman who developed recurrent skin lesions 3 years after the diagnosis of chronic myelogenous leukemia. Progression to an accelerated phase of the disease was detected 3 months after the beginning of the skin lesions. This case shows the convenience of evaluation and closer follow-up of patients with chronic myelogenous leukemia who develop skin lesions, especially if these lesions are recurrent. Received: 29 September 1999 / Accepted: 29 February 2000     

Busulfan/cyclophosphamide plus bone marrow transplantation is not sufficient to eradicate the malignant clone in juvenile chronic myelogenous leukemia

Bone marrow transplantation plays an essential role in the successful treatment of both juvenile and adult chronic myelogenous leukemia. Recently, it has been reported that conditioning with high doses of busulfan can successfully replace total body irradiation (TBI), in patients with acute myelogenous leukemia as well as adult chronic myelogenous leukemia. We report here the case of a 29-month-old boy with juvenile chronic myelogenous leukemia (JCML) transplanted with HLA-identical bone marrow after conditioning with busulfan, etoposide and cyclophosphamide. Successful engraftment was followed by early relapse on day 67. A second HLA-identical transplant was performed following myeloablative treatment with TBI. Engraftment was once again successful and the patient remains free of disease more than 24 months after transplantation. We conclude that busulfan is insufficient in eradicating JCML and that TBI is required prior to transplantation.     

Acute myelogenous leukemia complicated by compartment syndrome

A 37-year-old woman was diagnosed as having acute myelogenous leukemia. After obtaining complete remission by induction therapy, consolidation therapy was performed. She collapsed during an episode of chemotherapy-induced pancytopenia and developed compartment syndrome of the lower leg a week later. Fasciotomy was performed successfully, and she maintained her complete remission. Early diagnosis and fasciotomy are important in patients with leukemia complicated by compartment syndrome.     

Monoclonal antibody against a unique antigen on human acute promyelocytic leukemia cell line (HL-60)

An IgM kappa monoclonal antibody (WI-1) reacted against HL-60 cells in indirect immunofluorescence and microcytotoxicity tests. It failed to react against 19 other cell lines representing acute myelogenous leukemia, chronic myelogenous leukemia, lymphocytic leukemias, multiple myeloma, Burkitt's lymphoma, monocytoid cells and virus induced lymphoid cell lines. Normal peripheral blood nucleated cells and bone marrow cells derived from acute granulocytic leukemia, chronic granulocytic leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia also failed to react with WI-1. Normal peripheral blood lymphocytes, transferred with mitogens, showed no reaction against the antibody. There was some decrease in the reactivity of the cells, against WI-1, following maturation with dimethyl sulfoxide. However, a large percentage of the cells remained positive after maturation. WI-1 reacted specifically against an antigen on the HL-60 cells which had a molecular weight of about 42,000 dalton. Peripheral blood cells from one patient with acute promyelocytic leukemia failed to react with the antibody. It is possible that acute promyelocytic leukemia is an antigenically heterogeneous disease. A large population of acute promyelocytic leukemia patients needs to be tested to see if the specific antigen on HL-60 cells, detected by WI-1, is demonstrable in other patients with acute promyelocytic leukemia.     

Hairy cell leukemia responsive to anti-thymocyte globulin used as immunosuppressive therapy for aplastic anemia

Hairy cell leukemia (HCL) is occasionally misdiagnosed as aplastic anemia when only a few leukemic cells are present in the circulation. Here, we describe a patient with HCL who initially presented with pancytopenia and received a diagnosis of aplastic anemia. The patient was treated with immunosuppressive therapy including cyclosporine A and anti-thymocyte globulin (ATG). No blood cell transfusion was required for approximately 3 years after ATG therapy. She was referred to our hospital because of an abdominal mass and requiring periodic blood transfusions. A bone marrow biopsy at this time revealed proliferation of lymphocytes with a fried egg appearance and an increase in reticulin fibers that are typical findings of HCL. It is notable that our patient with a presumably long history of HCL and an increase in marrow reticulin fibers showed good recovery of hematopoiesis after cladribine therapy. Some HCL patients may receive an initial diagnosis of aplastic anemia and may show a good response to ATG masking the underlying HCL.     

Hematopoietic stem cell transplantation in children with hematological malignancies across HLA barriers--reasonable alternative?

The aim of this study was to evaluate the efficiency and risks of T-cell depletion in prevention of graft versus host disease (GVHD) using HLA haploidentical family donors as an alternative source of hematopoietic stem cells (HSC) in children with hematological malignancies without suitable matched donor. Ten children, median age 12 years (range, 3-17), were transplanted from haploidentical family donors for acute lymphoblastic leukemia (n = 4), acute myelogenous leukemia (n=2), chronic myelogenous leukemia (n = 2), non-Hodgkin lymphoma (n = 1) and myelodysplastic syndrome (n = 1). Parents were donors for nine, sibling for one patient. T-cell depletion of HSC was performed using CellPro followed by antiCD2/CD3 depletion in 7, and CliniMacs magnetic sorting in 3 grafts. Primary engraftment was achieved in nine patients. Patient with graft failure was successfully re-grafted. Primary acute GVHD was diagnosed in one patient who got higher amount of T-cells in the graft. Secondary GVHD was induced by add-backs of lymphocytes in four patients. Three patients developed chronic GVHD. Four patients died due to transplant related mortality (40%), one from veno-occlusive disease, two due to CMV pneumonia and one of aspergillosis with extensive chronic GVHD. Four patients relapsed with leukemia within 35-98 days post transplant, three without previous signs of GVHD, and all died. Two patients are alive and well 26 and 42 months after transplant. Haploidentical family donors appear to be a reasonable alternative option for patients with urgent indications for allogeneic transplant and/or without a matched donor.     

慢性中性粒细胞白血病5例临床分析

目的：探讨慢性中性粒细胞白血病（CNL）的诊断，治疗和预后。方法：对5例CNL患者的临床表现，实验室特点，治疗方法和预后进行分析。结果：5例CNL患者中，4例脾脏肿大；所有患者血液中中性粒细胞持续增多，骨髓粒系增生并以成熟中性粒细胞为主，中性粒细胞碱性磷酸酶（NAP）积分增高，Ph染色体或bcr/abl融合基因阴性；使用马利兰及羟基脲治疗后患者症状有所改善，脾脏缩小及血液中白细胞数下降；1例患者诊断后7年发生急性变。结论：CNL是一种少见类型的慢性白血病，其特点与慢性髓细胞白血病不同；马利兰及羟基脲对其有一定疗效；预后具有异质性。     

Pyomyositis as a Focus of Infection in Hematological Disorders: A Report of 3 Cases

The cases of 3 patients with pyomyositis associated with hematological disorders are reported. A 40-year-old man in the blastic phase of chronic myelogenous leukemia and 2 men aged 46 and 71 years with neutropenia due to myelodysplastic syndromes all reported high fever and severe local myalgia and had marked elevation of C-reactive protein. Magnetic resonance imaging revealed muscle abscesses or fasciitis, and the findings led to the diagnosis of pyomyositis. Methicillin-resistant Staphylococcus aureus was isolated from the abscesses of 2 patients, and surgical drainage proved more effective than did antimicrobial agents. It should be recognized that pyomyositis is a possible source of infection in patients with hematological disorders.     

The coexistence of chronic leukemia and pregnancy

The co-existence of pregnancy in 4 patients with chronic myelogenous leukemiahas been reported. One patient was known to have had chronic myelogenous leukemia 3 years prior to her pregnancy. The diagnosis of leukemia was made duringthe course of pregnancy in the remaining 3 patients; 1 in the first trimester, theother 2 in the third trimester. No specific therapy was required in any of the patients during pregnancy. Their children at birth showed no stigmata of leukemia.

Current literature on the subject has been reviewed. The consensus is that pregnancy does not influence the prognosis of chronic myelogenous leukemia. Duringthe period of gestation, the symptoms can be controlled by administration of asolution of potassium arsenite (Fowler’s solution) and irradiation therapy over longbones, spleen and mediastinum without exposing the fetus.

     

Transformation of myeloma into Ph1-negative CML with plasma cell antigens

We report a patient in whom Ph1-negative chronic myelogenous leukemia (CML) developed 15 years after the diagnosis of myeloma. Combined staining of morphologically myeloid elements in the peripheral blood for myeloid and plasmacytoid antigens revealed double-marker expression, suggesting that the two neoplasms arose from a common originator cell.     

Recurrent acute myositis after allogeneic bone marrow transplantation for myelodysplasia

A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia transformed from myelodysplasia. At the onset of myositis, the patient had oral dryness, and the histology of oral mucosa was compatible with chronic graft-versus-host disease (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine was increased. Three months later, a complete resolution of myositis had been obtained, and the cyclosporine was tapered off. However, 51 months after the first episode of myositis, she again noted severe myalgia and was diagnosed with a recurrence of polymyositis based on high serum creatinine kinase (CK) and the findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other organs was not present. She achieved a second remission of polymyositis with cyclosporine, and has remained in remission for 4 years. The pathogenesis of myositis can be attributed to the immunologic imbalance characteristic of the post-allogeneic BMT setting.     

Recurrent Acute Myositis after Allogeneic Bone Marrow Transplantation for Myelodysplasia

A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia transformed from myelodysplasia. At the onset of myositis, the patient had oral dryness, and the histology of oral mucosa was compatible with chronic graft-versus-host disease (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine was increased. Three months later, a complete resolution of myositis had been obtained, and the cyclosporine was tapered off. However, 51 months after the first episode of myositis, she again noted severe myalgia and was diagnosed with a recurrence of polymyositis based on high serum creatinine kinase (CK) and the findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other organs was not present. She achieved a second remission of polymyositis with cyclosporine, and has remained in remission for 4 years. The pathogenesis of myositis can be attributed to the immunologic imbalance characteristic of the post-allogeneic BMT setting.