Acute megakaryoblastic leukemia with leukemia cutis, meningeal leukemia, and myelofibrosis]

A 64-year-old man was admitted to our hospital with leukopenia. On admission, leukocyte count in the peripheral blood was 1,600/microliters, containing 24.5% blasts of lymphoid appearance, which were negative for myeloperoxidase. A bone marrow aspiration showed hypoplasia with increased blasts (31.6%). The blasts were ultrastructurally positive for platelet peroxidase (PPO) and positive for platelet membrane glycoprotein IIb/IIIa complex. A diagnosis of acute megakaryoblastic leukemia was made. Chemotherapy with behenoyl-ara C (BH-AC) (150 mg/day) was transiently effective. However, after three months, numerous nodules without itching appeared over the entire body, particularly on the anterior chest. A biopsy of the skin lesion revealed a diffuse fibrosis with infiltrations of the blasts. Bone marrow aspirations were dry tap, and a bone marrow biopsy showed marked myelofibrosis. Then, severe headache, vomiting, and loss of consciousness developed, and a lumbar puncture revealed infiltrations of blasts. Although methotrexate was intrathecally injected, he died due to the respiratory failure. As far as we know, a case of acute megakaryoblastic leukemia with leukemia cutis and meningeal leukemia is quite rare. In addition, it is interesting that megakaryoblastic leukemia was accompanied with both the fibrosis of skin and the myelofibrosis.     

Successful treatment of hairy cell leukemia with pentostatin

A 45-year-old woman was admitted to our hospital in August, 1999. Laboratory data showed a white blood cell count of 5,050/microliter with 78% abnormal lymphocytes, hemoglobin 6.8 g/dl, platelets 4.8 x 10(4)/microliter, and soluble IL-2 receptor 97,600/ml. The abnormal cells were characterized by a hairy appearance under phase contrast microscopy, and showed strong tartrate-resistant acid phosphatase activity. Immunophenotype analysis revealed that these cells were positive for CD11c, CD19 and CD25, and negative for CD5. Bone marrow biopsy showed diffuse proliferation of hairy cells with moderate myelofibrosis. We diagnosed the patient as having European-American-type hairy cell leukemia. Pentostatin was administered at a dose of 5 mg/m2 weekly. After twelve doses, the peripheral blood data returned to the normal range with no hairy cells in the blood or bone marrow, although slight splenomegaly remained. The patient underwent splenectomy in December of the same year, and we were unable to find any hairy cells by histological and immunohistochemical examination. Although most patients with hairy cell leukemia in Japan have the Japanese variant, and the European-American type is rare, pentostatin is as effective as it is for European and American patients.     

Plasma cell leukemia with myelofibrosis

Summary We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis improved with combination chemotherapy using vincristine, pirarubicin, and dexamethasone. However, when plasma cell leukemia became resistant to chemotherapies, myelofibrosis also reappeared. This case strongly suggests the pathogenetic relationship between plasma cell leukemia and myelofibrosis.     

Megakaryoblastic leukemia which developed from therapy-related MDS with myelofibrosis]

A 56-year-old man had a leiomyosarcoma of the small intestine in 1987. After surgery, he received cyclophosphamide for 2 years. In December, 1990, he exhibited severe pancytopenia. His hematological data were as follows: Hb 7.4g/dl, ret. 0.8%, WBC 1,700/microliters with leukoerythroblastosis and 2.8 x 10(4)/microliters platelets. A bone marrow aspiration was a dry tap. A bone marrow biopsy specimen showed a hypercellular marrow with myelofibrosis, leukemic infiltration (10.2%) and slight dyserythropoiesis. Both PPO and GPIIb/IIIa reaction were positive for blast cells and atypical megakaryoblasts. A diagnosis of MDS with an abnormality in megakaryocytic lineage was made. The patient was treated with 1,25-dihydroxy-vitamin D3, however this therapy was temporary and he developed into acute megakaryoblastic leukemia (M7). This report suggested that some cases of therapy-related leukemia (TRL) mainly involve megakaryocytic lineage and are diagnosed as MDS with myelofibrosis which transform to M7. The fact that PAS stain of erythroblasts in the patient reported here was positive may suggest involvement of development of more precise immunological markers of differentiation and EM study will permit better diagnosis of TRL and may therefore facilitate new therapeutic approaches.     

白血病继发网硬蛋白纤维化的骨髓活检研究

目的：平估骨髓活检在急、慢性白血病继发网硬蛋白纤维经的诊断价值。方法：Ｃ地比分析７６例急、慢性白血病多网硬蛋白纤维化的骨髓切片与涂片诊断结果，动态观察１０例急非淋患者化疗过程中网硬蛋白纤维量的变化情况，结果：风硬蛋白纤维可致白血病患者骨髓涂片假性增生低并引起误诊，活检可起作用正作用，伴骨髓纤维化和早期白血病发片能我早作出诊断，网硬蛋白纤维量的变化与白血病化疗疗效有关，结论：骨髓切片与涂片起互补作用     

Hairy cell leukemia successfully treated with deoxycoformycin]

A 45-year-old male was hospitalized on September 2, 1989 with chief complaints of general fatigue and fever. Physical examination revealed hepatomegaly and massive splenomegaly. Laboratory tests on admission showed Hb of 7.5g/dl, PLT 4.8 x 10(4)/microliters and WBC 9,610/microliters with 81% hairy cells. Bone marrow aspirate demonstrated 55.1% hairy cells and moderate myelofibrosis. Cytochemically, hairy cells were positive for tartrate-resistant acid phosphatase (TRAP). Surface markers were SmIg G+ A+ kappa +, CD11b+, CD11c+, CD19+, CD20+, CD21-, CD25+, HC2+, HLA-DR+. From these findings, a diagnosis of hairy cell leukemia (HCL) was made. After administration of deoxycoformycin (DCF) at a dose of 5.0mg/m2 1-2 times monthly, splenomegaly disappeared, as did hairy cells from the peripheral blood. Hematological level returned to within normal range except for the presence of 1.2% hairy cells and mild myelofibrosis in bone marrow aspirates. DCF has so far been effective for this patient. While DCF has been reported to be effective in the treatment of HCL in the West, it has not been determined in Japanese patients with HCL, who have different hematologic features from those of HCL patients in the West.     

Acute myelofibrosis. A report of four cases and review of the literature

Four new cases of acute myelofibrosis are reported, and 63 cases reported in the literature are reviewed. The typical features of this disease include a rapidly progressive clinical course; nonspecific symptoms such as weight loss, anorexia, fatigue and weakness; the absence of organomegaly; pancytopenia; circulating blast cells; and mild abnormalities in the red blood cell morphology. The bone marrow aspirates are usually "dry." The bone marrow biopsies are essential for the diagnosis and show four consistent features: hypercellularity, reticulin fibrosis, proliferation of blast cells and bizarre, atypical megakaryocytes. In 16 cases, the blast cells in peripheral blood and bone marrow, which are unclassifiable by conventional morphology, could be identified as megakaryoblasts by ultrastructural and immunocytochemical techniques. It is concluded that acute myelofibrosis is a definite clinicopathologic entity, which may be related to acute megakaryoblastic leukemia.     

Hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders (LPD-HC): the significance of morphologic, histologic and immunologic studies

In this report the clinical, morphologic, histologic and immunologic findings of 41 patients with hairy lymphoid cells in peripheral blood and/or bone marrow are analyzed. In 27 patients the diagnosis of hairy cell leukemia was established. 14 patients had other variants of lymphoproliferative disorders: malignant lymphoma with hairy cells--7, chronic lymphocytic leukemia with hairy cells--5, and T cell lymphoproliferative disorder with hairy cells--2 patients, respectively. Several variants of malignant lymphoma with hairy cells were defined: lymphocytic, centrocytic and lymphoplasmacytic. The importance of combined use of bone marrow biopsy and immunophenotyping for the correct diagnosis of hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders is stressed. The obtained data suggest relationship between characteristic clinical manifestation (isolated splenomegaly), presence of hairy cells and CD11c-antigen expression.     

Idiopathic myelofibrosis: a clinical study of 80 patients

A series of 122 consecutive patients with bone marrow fibrosis initially referred or categorized as idiopathic myelofibrosis is described. After a clinical and pathological review 14 patients were classified as postpolycythaemic myelofibrosis and 7 patients as a transitional myeloproliferative disorder. In 13 patients a diagnosis of hairy cell leukaemia was made, 3 patients had malignant lymphoma, 2 had malignant histiocytosis, and 1 patient had systemic lupus erythematosus with myelofibrosis. Two patients were excluded for further analysis owing to insufficient data. In the remaining 80 patients a diagnosis of idiopathic myelofibrosis was made. The clinical and laboratory findings in this series of patients are presented and compared to those in previous series. Infectious, cardiovascular, thromboembolic, and haemorrhagic complications were frequent, being recorded in 63%, 50%, 40%, and 33% of the patients, respectively. Various autoimmune phenomena were found in a proportion of the patients, but none had clinical evidence of connective tissue disease. Fifteen patients (19%) had a syndrome of acute myelofibrosis. The diagnostic criteria for this disease entity and its place within the spectrum of myeloproliferative disorders are discussed. In the present series acute myelofibrosis was found to encompass various transitional stages toward the evolution of acute leukaemia. It is proposed that acute or malignant myelofibrosis is considered as an acute variant of idiopathic myelofibrosis. Within this syndrome the acute variant seems to be far more common than previously recognized, which may also explain the marked clinical heterogeneity of the myelofibrosis/osteomyelosclerosis syndrome in this and most previous series.     

Cytogenetic findings in acute promyelocytic leukaemia A report of 25 cases

8 patients with clinical and haematological features suggestive of hairy cell leukaemia are described. During their initial illness morphologic and cytochemical evidence of hairy cell leukaemia were lacking in all but 2 patients. A common highly characteristic histopathologic finding was reticulin fibrosis in the bone marrow, present in all patients at first presentation. The term spongy lymphoid myelofibrosis is proposed for such cases, which may represent a variant type of hairy cell leukaemia or an early stage of the disease.     

European-American-type hairy cell leukemia without splenomegaly, treated successfully with deoxycoformycin]

A 55-year-old Japanese man was hospitalized on October 5, 1999, because of high fever. Physical examination revealed neither lymphadenopathy nor hepato-splenomegaly. Laboratory data on admission showed a white blood cell count of 1,580/microliter, a hemoglobin level of 9.1 g/dl, and a platelet count of 113 x 10(3)/microliter. A small percentage of abnormal mononuclear cells were present in the peripheral blood. A bone marrow biopsy specimen demonstrated myelofibrosis and diffuse infiltration of abnormal monoculear cells with a mature B cell phenotype. A bone marrow aspirate showed 29% abnormal mononuclear cells, which had an indented or folded nucleus and reticular nuclear chromatin. Moderate to strong tartarate-resistant acid phosphatase activity was detected in these cells. Although the cytoplasmic projections were poorly preserved in specimens stained with May-Giemsa, fresh preparations showed numerous slender cytoplasmic projections by phase-contrast microscopy. The hairy cells had the phenotype CD5-, CD10-, CD11c+, CD19+, CD20+, CD25+, lambda. The patient was diagnosed as having European-American-type hairy cell leukemia (HCL) without splenomegaly, which is quite rare in Japan. The value of phase-contrast microscopy for recognition of the hairy cells was emphasized. The patient was treated successfully with deoxycoformycin (DCF).     

The reversal of myelofibrosis associated with chronic myelogenous leukemia after allogeneic bone marrow transplantation

A 20-year-old male with chronic myelogenous leukemia (CML) and severe bone marrow fibrosis underwent splenectomy, then ablative chemotherapy, followed by bone marrow transplantation from a histocompatible sister. The myelofibrosis completely resolved. Prompt marrow engraftment and disappearance of Philadelphia chromosome positive cells were documented. Therefore, the presence of marrow fibrosis which frequently accompanies CML is rapidly reversible following high dose chemotherapy and is not indicative of a hostile microenvironment which could preclude marrow transplantation for patients with CML and myelofibrosis.     

Bone marrow histological modifications induced by alpha interferon in hairy cell leukemia

This paper reports the bone marrow histological picture in 7 patients with hairy cell leukemia treated with recombinant interferon. Bone marrow biopsies were performed at diagnosis, after 1, 3 and 7 months from the beginning of treatment and at 12 months at treatment suspension. The main modifications observed were a conspicuous reduction of hairy cell infiltrate, profound hypoplasia induced by the drug, early evidence of focal erythropoiesis followed by the appearance of other hematopoietic series and a progressive reduction of the reticulum. The clinical response to interferon therapy was good in all the patients studied; however future studies will have to evaluate the duration of response after treatment suspension.     

Development of hairy cell leukemia in a patient with antiphospholipid syndrome

We present a young woman who was diagnosed as primary antiphospholipid syndrome (deep vein thrombosis and pulmonary embolism in 1999; moderate thrombocytopenia with high-positive anticardiolipin ELISA tests in 2002, and cerebral thrombosis in 2003), and then developed hairy cell leukemia (massive splenomegaly, neutropenia, hairy cells in blood smear and bone marrow trephine biopsy in 2004). A partial remission was achieved with interferon-alpha 2a therapy. After the initiation of 2-chloro-deoxyadenosine therapy, splenomegaly disappeared, the percentage of hairy cells on the bone marrow reduced below 1%, platelet count returned to normal levels. After complete remission was achieved for hairy cell leukemia proved by bone marrow trephine biopsy, antiphospholipid antibodies were found to be negative, and no further thromboembolic complications and thrombocytopenia were seen. In our literature search, we found only six cases that had both antiphospholipid antibodies and hairy cell leukemia. Our case is the first case of antiphospholipid syndrome before the development of hairy cell leukemia. Both hairy cell leukemia and antiphospholipid syndrome responded to lymphocytotoxic treatment with 2-chloro-deoxyadenosine.     

The significance of paraproteinemia in hairy cell leukemia: case report and review of the literature

A case of hairy cell leukemia and IgG paraproteinemia is described. Peripheral blood surface marker analysis, serum paraprotein levels and immunoperoxidase stains of bone marrow sections at diagnosis and after 7 months of interferon treatment suggested the existence of two unrelated pathological B cell clones: one composed of malignant hairy cells and the other secreting the paraprotein. Previously reported cases of hairy cell leukemia with paraproteins are reviewed and our patient's contribution to the understanding of this association is stressed.     

Hairy cell leukemia presenting as a lupus-like illness

We describe a young Hispanic man who presented with features suggestive of a diagnosis of systemic lupus erythematosus. Eventually, a bone marrow biopsy was performed, and it revealed the presence of hairy cell leukemia. This case of a lupus-like syndrome should be added to the list of reported rheumatic syndromes that are associated with hairy cell leukemia.     

Dry tap bone marrow aspiration: clinical significance

Failure to obtain bone marrow on attempted marrow aspiration, "dry tap," has commonly been ascribed to faulty technique. All reports of simultaneous marrow aspirations and biopsies performed at the University of Virginia between January 1, 1983, and July 1, 1989, were reviewed to determine the frequency of dry taps, the diagnoses and pathologic findings in these cases, and the associated laboratory findings. Among 2,235 simultaneous bone marrow aspirations and biopsies, 87 were dry taps (3.9%). Of these 87 dry taps, only six (6.9%) showed normal marrow biopsies, whereas the majority showed significant marrow pathology, usually associated with fibrosis, or hypercellularity, or both. These conditions most likely account for the inability to aspirate marrow. The most frequent diagnoses were metastatic carcinoma (17.2%), chronic myelogenous leukemia (14.9%), idiopathic myelofibrosis (13.8%), and hairy cell leukemia (10.3%). The presence of peripheral blood nucleated red blood cells, thrombocytopenia, and elevation of the serum lactate dehydrogenase were frequent findings in patients who experienced dry taps. Methods to obtain sufficient marrow for rapid diagnosis in these cases are discussed.     

Hairy cell leukemia: a review.

Hairy cell leukemia is a chronic but steadily progressive malignancy usually of older males. Clinically, patients present with splenomegaly and/or cytopenia. The diagnosis is made by demonstration of the hairy cell in Wright's-stained peripheral blood and in bone marrow and by the characteristic histologic findings in the bone marrow biopsy and spleen sections. Infection is the most significant problem complicating the course of patients with hairy cell leukemia and the role of granulocytopenia and/or monocytopenia is undoubtedly substantial. Splenectomy has produced an objective response in improving hematologic parameters in a large number of patients and may prolong survival in those patients who respond. The precise nature of hairy cells remains unknown. The cells exhibit features of both monocytes and B-lymphocytes in morphologic, cytochemical, immunologic and functional studies. A more complete understanding of the monocytic and lymphocytic stem cells and their maturation may provide insight into the origin of the hairy cell.     

Systemic lupus erythematosus presenting with myelofibrosis.

The 20-year-old girl we describe presented with myelofibrosis and systemic lupus erythematosus (SLE), which initially responded to treatment with corticosteroids but during a relapse 9 months later a bone marrow biopsy revealed no improvement in her myelofibrosis. As the cytotoxic treatments used to treat severe SLE may be associated with bone marrow suppression, it is important to consider the possibility of myelofibrosis complicating SLE, which, even when it is a presenting feature, may not readily respond to corticosteroids. When this girl was subsequently treated with high dose steroid and azathioprine her myelofibrosis went into remission.     

Acute vasculitis as a first manifestation of hairy cell leukemia

Hairy cell leukemia (HCL) is a lymphoproliferative malignancy characterized by bone marrow, spleen, liver, and occasionally lymph node infiltration with hairy cells, usually accompanied by splenomegaly and pancytopenia. We report an unusual case of HCL in a 53-year-old woman with leukopenia and sudden onset of fever of unknown origin, arthritis, and generalized maculopapular exanthem. Skin biopsy revealed perivascular and/or vessel wall lymphocytic infiltration in the dermis. On the basis of bone marrow biopsy and flow cytometry, the diagnosis of HCL was established. A detailed, retrospective re-evaluation of the skin biopsy helped to identify hairy cells among the cells of the perivascular infiltrations. Small-vessel vasculitis, as an atypical presentation, was found to predate a diagnosis of HCL. Recognition that vasculitis can reflect or antedate lymphoid malignancy may permit early diagnosis and aggressive treatment. A rapid response was obtained with a single course of cladribine.