Bone marrow necrosis in acute leukemia

2 patients with premortem marrow necrosis in acute leukemia are discussed. A review of the course of each patient plus those in the literature suggests that premortem marrow necrosis may not be a poor prognostic sign in acute lymphoblastic leukemia but generally precedes a prolonged and fatal pancytopenia in acute myelogenous leukemia. The technetium-99m rhenium sulfur colloid marrow scan was found to be of value in assessing the extent and degree of necrosis of the marrow as well as in documenting and predicting marrow recovery following chemotherapy.     

Bone marrow necrosis. acute microcirculation failure in myelomonocytic leukemia.

We saw bone marrow necrosis in a case of acute myelomonocytic leukemia. The diagnosis was made during the patinet's life, and the bone marrow microcirculation was studied immediately postmortem. Histology and injection of the bone marrow arteries showed an acute microcirculation failure. The pathogenesis and possible relationship with soluble immune complexes was studied.     

Bone marrow plasmocytosis in acute leukemia

A quantitative evaluation of IgA, IgD, IgG and IgM plasmocytes in sequential bone marrow aspirates of patients with acute leukemia using the peroxidase-antiperoxidase method was undertaken. Plasmocytosis resembled that of normal controls or was slightly subnormal on admission. When remission was obtained, bone marrow plasmocytosis was similar to normal controls, irrespective of the type of acute leukemia and the cytostatic treatment. Occurrence of infection strongly augmented the number of plasmocytes, with an initial increase in IgM and later in IgG plasmocytes. This suggests that the immune response is preserved in patients with acute leukemia.     

Bone marrow fibroblasts in acute lymphoblastic leukemia

Fibroblast-like cells were grown from the bone marrow of acute lymphoblastic leukemia (ALL) patients before, during and off therapy. A diminished growth capacity was observed in cells from patients before and during therapy. In the three groups studied, differences were also observed in the effect of hydrocortisone on DNA synthesis and in the content of glucocorticoid binding sites. These results suggest that microenvironmental changes occur in ALL, which may revert to normality during or after therapy.     

骨髓移植治疗急性白血病的最新进展

近年来随着新的化疗药物不断问世、联合化疗方案设计不断改善和支持治疗手段的增多 ,使急性白血病的缓解率有了进一步提高。目前 6 0岁以下成人初治急性非淋巴细胞白血病经联合化疗可使 70 %～ 80 %患者达到完全缓解 (ＣＲ) ,成人急性淋巴细胞白血病ＣＲ率可达 6 4%～ 87% ,但绝大多数患者若用常规化疗巩固和强化治疗 ,最终将会复发 ,复发后治愈希望甚微。骨髓移植 ,尤其是异基因骨髓移植是目前治愈急性白血病最为有效的手段 ,本文重点简述近年来骨髓移植 (异基因骨髓移植和自体骨髓移植 )治疗急性白血病的进展情况。1　急性白血病异基因骨…     

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.     

Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide

Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.     

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.     

Bone marrow karyotypes in 94 children with acute leukemia

During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T-cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T-cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.     

Bone marrow necrosis.

The clinical findings of bone marrow necrosis in 13 patients undergoing bone marrow examination to investigate a peripheral blood cytopenia or leukoerythroblastic blood smear were reviewed and compared to those in the literature. Excluding sickle cell disease, all cases of bone marrow necrosis diagnosed during life were associated with a neoplastic process involving the marrow. A myeloproliferative disorder was found in five patients, metastatic carcinoma in five patients, a lymphoma in two patients, and both a myeloproliferative disorder and metastatic carcinoma in one patient. Marrow necrosis was found to involve the marrow at multiple sites in a piecemeal fashion with areas of necrotic marrow and structurally intact marrow adjacent to each other. Severe bone pain without roentgenographic abnormality was the major symptom in 85% of the patients. Marrow and fat emboli, hypercalcemia and peripheral blood cytopenias were identified as direct complications of marrow necrosis. The prognosis of patients with marrow necrosis secondary to neoplastic disease was found to be extremely poor with a median survival of less than one month. However, one patient responded to antineoplastic chemotherapy and showed healing of the bone marrow.     

Marked bone marrow necrosis preceding acute myeloblastic leukemia in childhood

A 3-year-old boy was transferred to our hospital because of fever, abdominal pain and severe systemic bone pain on October 16, 1989. Hematological examination showed hemoglobin 8.7 g/dl, white blood cell count 5300/microliters with 9% neutrophils and platelet count 5.5 x 10(4)/microliters. Bone marrow aspiration and biopsy revealed markedly necrotic cells. Blood chemistry showed transient elevation of CRP, serum LDH, FDP, FDP-Ddimer and fibrinogen. Tc99m pyrophosphate bone scanning showed multiple uptake spots in various bone. Although the sign of fever, abdominal pain and bone pain disappeared spontaneously after three weeks, anemia persisted. About two months later from bone marrow necrosis, abnormal cells appeared in the bone marrow. A diagnosis of AML (M3) was made and a combination chemotherapy started. This case is remarkable for elevation of acute phase protein in association with bone marrow necrosis.     

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.     

Bone marrow transplantation following busulfan and cyclophosphamide for acute myelogenous leukemia

Twenty-five consecutive patients with acute myelogenous leukemia (AML) underwent 26 allogeneic bone marrow transplants at Hahnemann University Hospital. Marrow ablation for all patients consisted of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BUCY2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methylprednisolone. Seventeen transplants were performed during first remission and the rest during subsequent remission or relapse. All patients engrafted and all but one achieved a complete remission (CR) following a short period of aplasia. Twenty-two of 25 patients are alive. All 17 patients with AML transplanted in first CR are alive and 15 of these patients are in sustained hematologic remission with an estimated 2-year disease free survival of 85%. The estimated 2-year disease free survival is 70% for all patients followed for a median of 622 days (range 134-1533). Acute GVHD of grades 2-4 occurred in 23% of these patients. Toxicities of the regimen including interstitial pneumonitis, veno-occlusive disease (VOD) and hemorrhagic cystitis were minimal. There were no treatment related deaths. These results demonstrate that BUCY2 should be considered as a preparative regimen for allogeneic bone marrow transplantation for patients with AML in first remission.