Bone marrow necrosis and degeneration.

Bone marrow necrosis, regarded as a rare finding in specimens from living patients, has been associated with a poor prognosis in patients with serious hematologic diseases and metastatic carcinoma. Two patients with extensive idiopathic bone marrow necrosis and a relatively benign course of illness were found. Therefore, we examined 500 consecutive bone marrow biopsy specimens that were obtained in a university hospital complex. Review of this material showed evidence of necrosis and degenerative changes of variable severity in one third of the biopsy specimens. It was found with approximately the same incidence in patients who underwent bone marrow biopsy for either neoplastic or nonneoplastic disorders; an increased prevalence was not observed in the group of patients who had received chemotherapy. Based on these observations, we believe necrosis and degeneration of the bone marrow is a commonplace finding that is frequently overlooked in a wide variety of acute and chronic disorders, and that requires further investigation to determine its clinical importance.     

Pancytopenia due to bone marrow necrosis in acute myelogenous leukemia: Role of reactive CD8 cells

Bone marrow necrosis is a rare clinical condition often associated with hematological malignancy. The mechanism by which malignant disease causes marrow necrosis is unknown. We present a case of a patient with newly diagnosed pancytopenia with bone marrow biopsy evidence of extensive marrow necrosis. Upon further work-up utilizing Tc bone scan directed bone marrow biopsy, a massive CD8+ T cell marrow infiltrate was discovered engulfing AML-M2 blasts. The role of Tc bone scans in the work-up of bone marrow necrosis as well as the potential mechanism of AML-M2 induced marrow necrosis in the setting of reactive CD8+ T cell infiltration is discussed. Am. J. Hematol. 59:74– 78, 1998. © 1998 Wiley-Liss, Inc.     

Pediatric acute lymphoblastic leukemia initially presenting with bone marrow necrosis

We report on a case of pediatric acute lymphoblastic leukemia presenting with massive bone marrow necrosis. A 4-year-old boy complained of fever and leg pain. Laboratory data revealed pancytopenia, but bone marrow examination showed only necrotic materials. About one month later, repeated bone marrow examination showed leukemic cells and the necrotic marrow had disappeared. The patient was treated with standard chemotherapy and was successfully induced to complete remission. Patients with massive bone marrow necrosis should undergo bone marrow examination repeatedly to make the correct diagnosis.     

Acute unclassified leukemia with bone marrow necrosis

Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.     

骨髓检查在临床诊断中的价值：附722例分析

目的 :探讨骨髓像对临床 ,尤其是血液病诊断的意义。方法 :结合 72 2例骨髓穿刺检查结果进行回顾性分析 ,其中 2 10例进行了骨髓活检。结果 :对各类型白血病、多发性骨髓瘤、骨髓转移癌、部分恶性组织细胞病及疟疾可确诊。可协助增生性贫血、再障等疾病的诊断及与某些疾病的鉴别诊断。结论 :骨髓检查、周围血检查及临床资料对诊断血液系统疾病、感染性疾病是重要的     

Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid

All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m²), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, non-infarcted bone trabeculae. We postulate that the development of bone marrow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL. © 1994 Wiley-Liss, Inc.     

Malignancy: Case Report: Hypereosinophilia Progressing to Granulocytic Sarcoma and Acute Myelocytic Leukemia with Trisomy 8: A Case Report and Review of the Literature

Conditions associated with increased peripheral blood and bone marrow eosinophil count may be reactive, clonal or idiopathic. Clonal eosinophilic disorders are characterized by increased production of eosinophils alongside a clone of malignant cells. In these patients, the eosinophils can either be demonstrated as being part of the malignant clone or produced as a result of cytokine production by the malignant clone. Criteria for the diagnosis of idiopathic hypereosinophilic syndrome (HES) include the exclusion of other known causes of hypereosinophilia. A few patients with the initial diagnosis of HES develop clonal disorders manifested by granulocytic sarcoma or acute leukemia. We report a patient with a nine year history of HES before progressing to chloroma and acute leukemia. Cytogenetic studies on the bone marrow specimen revealed trisomy 8. This report and others in the literature support the concept that at least some cases of HES are as yet unidentified clonal diseases. Cytogenetic studies are therefore recommended at diagnosis and during the follow up of patients with HES.     

Bone Marrow Findings in Infectious Mononucleosis and Mononucleosis-Like Diseases in the Older Adult

The bone marrow findings in 5 older adults with infectious mononucleosis or mononucleosis-like illnesses are presented. These individuals were initially considered to have lymphoproliferative disorders which often have similar constitutional signs and symptoms. All had atypical lymphocytosis of the peripheral blood. In addition, there were also abnormalities in the bone marrow. The most common findings included focal collections of lymphocytes and the presence of granulomas. The granulomas were small without caseous necrosis and giant cells were infrequent. This is in contrast to the idea that the bone marrow is normal in infectious monoculeosis and gives support to performing core biopsies as the aspirate smears in these individuals did not demonstrate the focal lymphocytosis or granulomas. Whereas, infectious mononucleosis and mononucleosis-like illness may be uncommon in the older individual, they certainly are not rare and it is important to differentiate these benign disorders from the more serious lymphoproliferative diseases. Heterophil test and/or Epstein Barr titers are important confirmatory tests.     

Improvement of bone marrow hematopoiesis in idiopathic myelofibrosis with prednisolone]

A 64 year-old female patient of idiopathic myelofibrosis (IMF), who had had rapidly progressing massive splenomegaly and severe pancytopenia refractory to blood transfusion, was treated with PSL 0.6 mg/kg/day for a month, being significantly improved not only symptomatically and hematologically but also in bone marrow hematopoiesis. Although the effectiveness of PSL to restoration of bone marrow hematopoiesis has been almost unknown, long term oral PSL should be tried for a certain phase of IMF.     

Unexplained bone marrow granulomas: Is amiodarone the culprit? A report of 2 cases

Granulomas in the bone marrow are usually caused by infectious or hematological diseases, and drugs are only rarely implicated as causative agents. Recent reports have drawn attention to the role of amiodarone in the etiology of bone marrow granulomas. We report two cases of amiodarone-induced bone marrow granulomas in patients being investigated for refractory anemia and pancytopenia, respectively. Since both patients had life-threatening arrhythmias, discontinuation of the drug followed by rechallenge was not possible. Both patients did well in spite of continued amiodarone therapy, indicating that the underlying hematological illnesses were unrelated to the granulomas. Amiodarone should be considered as a possible cause of bone marrow granulomas after the exclusion of other causes. Continued use of amiodarone after granuloma formation must be dictated by the underlying cardiac condition.     

Bone marrow necrosis in malignant diseases. A report on seven intravitally recognized cases

Bone marrow necrosis (BMN) is a necrosis of the hemopoietic tissue including the fibrovascular medullary stroma. Most frequently, it is caused by failure of bone marrow microcirculation. It is a complication in a wide spectrum of diseases, most frequently of malignancies, and is only rarely diagnosed ante mortem. In 6 of our 7 intravitally diagnosed cases, BMN was recognized already at the cytological examination of the bone marrow and was verified by the histological examination of the biopsy specimens as well as at necropsy. All our patients suffered from various malignant diseases. Three had generalized gastric carcinoma, the remaining hematological neoplasias: Acute lymphoblastic leukemia, acute monocytic leukemia, blastic transformation of chronic granulomegakaryocytic myelosis and primary medullary centrocytic lymphoma. The survival varied from 4 to 14 weeks after the BMN diagnosis. Clinical, hematological and autopsy findings as well as the etiopathogenetic views and prognostic implications of the diagnosis are discussed.     

Bone marrow necrosis

Bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with poor prognosis. In contrast, we believe that it is a commonplace finding in bone marrow specimens which is frequently overlooked and which occurs in patients with multiple acute and chronic disorders. It is postulated that bone marrow necrosis eventuates from vascular occlusion of small blood vessels as a result of a number of causes. When bone marrow necrosis is prolonged, it may be associated with the development of bone marrow fibrosis and serve as a predisposing lesion for idiopathic myelofibrosis. Additional investigation of this phenomenon is required to determine its usefulness in the diagnosis of disease states and its role in the pathophysiology of a number of disorders.     

Minor bcr/abl positive acute lymphoblastic leukemia preceded by knee joint pain due to bone marrow necrosis

A 16-year-old male was referred to our hospital in April 2003 due to severe knee joint pain from five months previously. Lymphoblasts were identified in his peripheral blood, resulting in a diagnosis of acute lymphoblastic leukemia (ALL). Bone marrow examination revealed massive necrosis with clusters of lymphoblasts and the bcr/abl fusion gene. Magnetic resonance imaging (MRI) of the knee joint showed low signal intensity on T1-weighted images, and peripheral rim enhancement on Gd-DTPA enhanced fat suppression images, which was compatible with bone marrow necrosis. After the patient achieved complete remission (CR), the knee joint pain has disappeared. He was treated with an allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor and has been in CR for 26 months after the diagnosis of ALL. In the knee joint, the replacement of fatty marrow after BMT has been confirmed with MRI. Hematological malignancies including ALL should be considered in the cases of bone marrow necrosis and adequate treatment may improve necrosis.     

Chronic idiopathic myelofibrosis. A reversible disease?.

A patient with chronic idiopathic myelofibrosis was subjected to splenectomy 1 year after diagnosis. As a clinically unexpected finding, lymph node biopsy suggested the presence of non-Hodgkin lymphoma. The patient was subjected to intensive combined cytostatic therapy. In the following months, signs and symptoms of myelofibrosis regressed remarkably. The patient died 31 months after splenectomy in massive gastrointestinal bleeding. At post-mortem, myelofibrosis could not be detected in three bone marrow areas and a regular, fat-containing, hypercellular marrow was present. The nature of the previous lymph noede pathology was reconsidered, and angioimmunoblastic lymphadenopathy was diagnosed.     

Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy

Treatment of autoimmune disease with bone marrow transplantation (BMT) is under investigation. A few reports of patients undergoing allogeneic BMT for malignant conditions observed the resolution of psoriasis after BMT, with minimal late morbidity. We describe a patient with chronic myelogenous leukemia (CML) whose psoriasis resolved completely after allogeneic BMT. However, the patient's course was complicated by extensive chronic graft-versus-host disease (GVHD), recurrent serious infections, poor performance status and quality of life, and severe disability. The patient died 887 days post transplant due to infectious complications. The potential benefits and risks of treatment of autoimmune diseases with allogeneic BMT are discussed.     

Local implantation of autologous mononuclear cells from bone marrow and peripheral blood for treatment of ischaemic digits in patients with connective tissue diseases

OBJECTIVE: CD34-positive bone marrow mononuclear cells (MNCs) have been successfully used for regeneration of small arteries in Buerger's disease. The objective of this study is to examine the angiogenetic potential of autologous MNCs from bone marrow and peripheral blood implanted into the ischaemic digits from patients with connective tissue diseases. METHODS: Three patients with systemic sclerosis, two with mixed connective tissue disease, and one with CREST syndrome were enrolled who had painful ischaemic digits with necrosis refractory to several vasodilators including intravenous prostaglandins. MNCs obtained from 7 ml/kg bone marrow blood and 400 ml peripheral blood were implanted into 20 different sites in palms and/or soles. The study was performed open-labelled. RESULTS: Pain in the numeric rating scale improved remarkably up to 1 month after implantation of bone marrow or peripheral MNCs to the same extent, although no significant differences were found in transcutaneous oxygen pressure and thermogram before and after the implantation. Bone marrow MNCs increased blood flow of the hand determined by intra-arterial digital subtraction angiography, while peripheral MNCs did not. CONCLUSIONS: Implantation of autologous MNCs from peripheral and bone marrow into the ischaemic digits was so effective in pain-relief and more clinical trials would be warranted to see whether this could be a new treatment modality for angiogenesis in connective tissue diseases as in Buerger's disease.     

Bilateral trephine bone marrow biopsies in lymphoma and other neoplastic diseases.

We have evaluated the usefulness of bilateral rather than unilateral posterior iliac spine trephine biopsies in searching for lymphoma and other neoplastic diseases in the bone marrow. Two hundred and eighty-two patients with these diseases were studied. Tumor was found on only one side in 22% of patients with non-Hodgkin's malignant lymphoma, in 43% of patients with Hodgkin's disease, and in 36% of patients with other neoplastic processes. Thus, the second biopsy yields an additional 11% to 22% of positive biopsies. We conclude that bilateral trephine bone marrow biopsies should be routinely performed when searching for tumor in the bone marrow.     

Clonal eosinophilia revealed by recurrent Staphylococcus aureus infection

Acquired eosinophilia is currently classified into secondary (reactional to underlying diseases), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories. We report the case of a 47-year-old male who was admitted to the hospital for Staphylococcus aureus recurring infections. An hypereosinophilia was discovered and led to molecular analysis. The identification of FIP1L1-PDGFRA fusion gene permitted the diagnostic of clonal eosinophilia. Treatment by imatinib mesylate induced an haematological remission, the control of the infection and thoracotomy cicatrization. This case is original because of its infectious presentation and the efficacy of imatinib mesylate to control the infectious process.     

Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center

In children, pulmonary sequelae contribute to early and late morbidity after bone marrow transplantation (BMT). Between 1975-1999, we performed 152 BMTs in 138 pediatric patients with malignant and nonmalignant diseases. Allogenic bone marrow was used from 99 HLA identical siblings and from 23 other related or unrelated donors. Autologous marrow was used in 30 transplantations. Median age was 8. 6 years (range, 1.1-22.4) at time of BMT. The median survival was 42%, the survival time was 6.5 years (range, 0.8-23.1), and the median follow-up time was 6.8 years (range, 0.8-23.2). Seventeen patients had severe respiratory complications. Early severe respiratory complications leading to death within the first 4 months after BMT were due to pulmonary edema (n = 1), or fungal (n = 3), bacterial (n = 1), or viral (n = 2) pneumonia. Late severe respiratory sequelae were defined as persistent respiratory symptoms for more than 4 months despite treatment, and these occurred in 10 patients, of whom 5 died. Underlying diagnoses covered a wide spectrum, including bronchiolitis obliterans (n = 3), severe restrictive lung disease (n = 2), idiopathic pneumonia syndrome (n = 3), chronic bronchitis (n = 1), and hepatopulmonary syndrome (n = 1). The overall probability for death was 0.58, and for death from severe respiratory complications, 0.16. With improved HLA matching, fewer BMTs after relapsed or primary progressive disease, and improved supportive care, including the usage of CMV negative blood products, after 1990 the probability of death from severe respiratory complications was only 0.04, whereas before 1990 it was 0.23 (P = 0.029; in each time period, n = 69). The disease spectrum has changed from initially more infectious complications to bronchiolitis obliterans and idiopathic pneumonia syndrome. Lung function measurements performed in 85 of 138 patients usually showed a mild restrictive pattern. To identify those children as early as possible who are at risk for severe respiratory complications, a close longitudinal follow-up after BMT by pediatric pulmonologists is necessary.     

The use of polyclonal intravenous immunoglobulins in the prevention and treatment of infectious diseases

In this review we discuss the prevention and treatment of infectious diseases with intravenous immunoglobulins (IVIG). IVIG can be used to prevent infections in primary as well as in certain secondary immunodeficiencies. We also discuss the use of IVIG in the prevention of CMV-disease after organ or bone marrow transplantation. Besides their use in prevention, IVIG can also be used as an additional therapy in sepsis in neonates, in streptococcal toxic shock syndrome and in CMV-disease after bone marrow or solid organ transplantation. We briefly discuss the different preparations of IVIG that are available in Belgium.