Recovery from widespread bone marrow necrosis occurring after chemotherapy for adult acute monocytic leukemia

A patient with acute monocytic leukemia who developed bone marrow necrosis following induction chemotherapy is presented. Although the bone marrow necrosis was extensive, recovery occurred, along with complete remission of leukemia. Severe bone marrow necrosis in this setting may be reversible, and continued vigorous supportive care for these patients should be strongly considered. © 1992 Wiley-Liss, Inc.     

Avascular necrosis of bone following combination chemotherapy for acute lymphocytic leukemia

Avascular necrosis of bone (AVNB) is a known complication of systemic adrenocorticosteroid therapy, and one which is thought to be dose-related. However, despite the large amounts of prednisone which have been used in the standard treatment of acute lymphocytic leukemia (ALL), AVNB rarely has been reported in children with that disease. We described our experience with one adolescent with ALL who developed multifocal AVNB presenting as bone pain after aggressive chemotherapy that included a high cumulative dose of corticosteroids as well as other antitumor agents, some of which also have been associated with AVNB. Four similar cases from the literature are reviewed. Because the bone pain of AVNB can mimic that of leukemic relapse, this is an important entity to be aware of, and one which may become more common with increasingly aggressive combination chemotherapy.     

Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia

BACKGROUND: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy. PROCEDURE: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT. RESULTS: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse. CONCLUSIONS: This regimen is toxic but effective and deserves study in a larger setting.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia.

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Bone marrow necrosis foreshadowing acute lymphoid leukemia

Necrosis of the bone marrow is rarely observed during life. Less than 50 cases have been reported, for the most part in patients with leukemia. The finding of bone marrow necrosis in children is even more rare. Of the seven cases reported, six patients had acute lymphoid leukemia and one patient had lymphocytic lymphoma. The occurrence of marrow necrosis diagnosed by aspirate and by biopsy in a child 18 months of age is presented. The necrosis was present several months before the appearance of acute lymphoid leukemia. The reasons for the presumed rarity of this pathological finding, its relationship with bone or joint pain and fever, hypotheses concerning pathogenesis, and its prognostic value are discussed.     

以骨髓坏死为特征的幼儿急性淋巴细胞白血病1例

男,2岁。因发热10d,面色苍黄、骨骼疼痛2d 入院。患儿10d前无明显诱因出现不规则发热,体 温达38℃～39℃,伴乏力、食欲差。2d前体温升到 39.5℃,并出现面色苍黄、多处骨骼疼痛,血常规示: 血红蛋白86g/L,白细胞11.2×109/L,血小板64× 109/L,予抗感染治疗2d无效入院。查体:体温 39℃,急性热病容,中度贫血貌,面色苍黄,结膜、甲 床苍白,足背部、肩部可见少量针尖大小出血点,颌 下、颈部可触及2粒黄豆大小淋巴结,质软,活动度 可,无压痛,其余浅表淋巴结未触及。肝肋下 2.5cm,脾肋下2cm,质中、边缘钝。胸骨、四肢骨 骼及指骨、趾骨有明显压痛。…     

Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden

All children in Sweden who underwent bone marrow transplantation (BMT) with an HLA-identical sibling during a 5-year period were compared to those who were treated with chemotherapy and survived at least 3 months after remission. All patients were observed for more than 2 years after diagnosis or relapse. All 11 children with acute myeloid leukemia in first remission who underwent BMT survived compared to only 1 of 15 treated with chemotherapy (p less than 0.001). In children with acute lymphoblastic leukemia (ALL), those relapsing while on chemotherapy and treated with BMT in second to fourth remission (n = 16) had a 5-year survival of 43% compared to 16% for those treated with chemotherapy (n = 53, p less than 0.05). In children with ALL relapsing after cessation of therapy, 4-year survival was 33% for BMT (n = 6) and 55% for chemotherapy (n = 15), p = 0.05).     

Localized bone marrow relapse in acute lymphoblastic leukemia.

Localized bone marrow relapse is rare in acute lymphoblastic leukemia. Discordant bone marrow specimens were found in an 11-year-old asymptomatic girl who had been in remission for six years and off chemotherapy for 2 1/2 years. One bone marrow sample showed marked leukemic infiltration, whereas marrow from another site was normal. Three months later, with normal peripheral blood counts, she developed severe back pain and x-ray evidence of vertebral collapse and periosteal changes in the pubic bone. At that time three of the four areas of bone marrow sampled showed leukemic involvement. Reinduction therapy was begun, and she is now in remission on maintenance chemotherapy. At this time, it is unclear whether routine performance of marrow aspirations and biopsies from multiple sites, in periodic follow-up examinations of patients with acute leukemia would allow earlier detection of relapse frequently enough to justify the procedure. The issue of localized bone marrow involvement, if more common than previously reported, should be addressed at the time a decision is being made to discontinue therapy.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Longitudinal gonadal function after bone marrow transplantation for acute lymphoblastic leukemia during childhood

Total body irradiation and high-dose chemotherapy, applied as a preparatory regimen for bone marrow transplantation (BMT) in children with acute lymphoblastic leukemia (ALL), are particularly hazardous to the gonads and, in addition, can impair hypothalamo pituitary-gonadal control. Longitudinal data on pubertal development and gonadal function in these patients are limited. Twenty-one ALL patients (15 males, 6 females) who had successfully undergone allogeneic BMT before puberty (age at BMT: 3.4-12.3 yr) were followed up in University Children's Hospital, Tübingen, Germany over 2 (minimum) to 14 (maximum) years. Tanner development scores, serum testosterone and estradiol, basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were analyzed. During pubertal age, the levels of FSH and LH rose consecutively, resulting in noticeably elevated serum concentrations in 100% and 89%, respectively, of boys older than 14 years and in 75% and 75%, respectively, of girls older than 13 years. Nevertheless, pubertal development has been normal in all patients except in one boy and two girls who required substitution with sexual steroids, as timely puberty (i.e. boys < 14 years, girls < 13 years) did not start. In males with normal puberty, testosterone levels, however, were found to be low-normal. In conclusion, after BMT preceded by total body irradiation for childhood ALL, gonadal function is impaired. Even if normal pubertal development occurs, deficiencies in long-term endocrine function cannot be ruled out. In view of the high FSH levels, the prognosis for fertility is doubtful.     

Bone marrow transplantation for acute monocytic leukemia following the treatment of Hodgkin's disease

A 32-year-old woman developed acute monocytic leukemia within a year of treatment for Hodgkin's disease with chemotherapy and radiation. Residual leukemia was present in the bone marrow after two induction courses of high-dose Ara-C. She received a bone marrow transplant from an HLA- and DR-identical sister and remains in complete remission more than 2 years after transplantation. Only one other instance of a remission greater than 2 years after transplantation for secondary acute leukemia could be found in the literature. Although bone marrow transplantation may be carried out successfully in these patients, it is possible that they may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation. Only further study can clarify this matter and determine the best time for the procedure and which regimen should be used.     

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow for acute lymphoblastic leukemia

Ten patients age 13–52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily × 4 and total body irradiation 3 Gy daily × 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100–120 μg/mL. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 ± 0.7 × 10⁸/kg, and the CFU-GM content of the transplant was 0.4 ± 0.5 × 10³/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 × 10⁹/L at a median of 26 days and platelets exceeded 50 × 10⁹/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2–9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43 +, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.     

Presentation and outcomes for children with bone marrow necrosis and acute lymphoblastic leukemia: a literature review

Bone marrow necrosis is a rare histopathology finding with the majority of cases occurring in the setting of a hematologic malignancy. This article reports a case of diffuse marrow necrosis in a child secondary to acute lymphoblastic leukemia and summarizes the clinical features and outcomes for children with bone marrow necrosis secondary to leukemia from 20 published reports. This review demonstrated that the most common presenting features were bone pain, fever, pancytopenia, and that outcomes were less favorable when compared with those without necrosis. However, contemporary literature suggests that outcomes are similar for children who have bone marrow necrosis secondary to leukemia when compared with overall survival rates for pediatric leukemia.     

Bone marrow necrosis and thrombotic complications in childhood acute lymphoblastic leukemia.

Two children with bone marrow necrosis at diagnosis or at relapse of acute lymphoblastic leukemia (ALL) had thrombotic complications 15 and 17 days after starting remission induction therapy including prednisone, vincristine, and L-asparaginase. The close temporal relationship of these two relatively rare events suggests that bone marrow necrosis is a predisposing factor to the development of thrombosis.     

Avascular necrosis of bone in acute lymphoblastic leukemia

Avascular necrosis of bone (AVNB) is a known complication of systemic adrenocorticosteroid therapy and is thought to be dose related. However, despite the large amount of prednisolone that has been used in the standard treatment of acute lymphoblastic leukemia (ALL), AVNB has rarely been reported with this disease. We have described our experience with an adolescent girl with ALL who developed multifocal AVNB after aggressive chemotherapy, which included high cumulative doses of corticosteroids along with other cytotoxic drugs, some of which have been associated with AVNB. Five similar cases from literature are reviewed. The occurrence of AVNB may become more common in the future with the increasing use of aggressive chemotherapy. Awareness of this possibility will lead to a more rapid diagnosis and early treatment of AVNB.     

Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse

BACKGROUND: Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL. PROCEDURE: Thirty pediatric patients with relapsed medullary (n = 18) and extra-medullary (n = 12) ALL were enrolled at three pediatric institutions. Following receipt of induction and the first Block A and Block B of intensification, each patient was evaluated for toxicity, efficacy in achieving remission, and long-term survival. Additionally, minimal residual disease (MRD) detection by multidimensional flow cytometry (MDF) was performed. RESULTS: During induction, the major non-hematopoeitic toxicities were mucositis (30% of patients) and bacteremia (50% of patients). Two patients (7%) died of toxicity during induction. Toxicity during intensification Block 1A and 1B was markedly reduced. Eight-nine percent of patients with marrow disease achieved a remission following induction and intensification. The event-free survival (EFS) for all patients at 2 and 4 years were 60% (95% CI: 42-78%) and 49% (95% CI: 30-68%), respectively. CONCLUSIONS: This regimen for patients with relapsed ALL was successful in achieving a second remission for the majority of patients with acceptable toxicity.     

Localized bone marrow relapse in acute lymphoblastic leukemia

Localized bone marrow relapse is rare in acute lymphoblastic leukemia. Discordant bone marrow specimens were found in an 11-year-old asymptomatic girl who had been in remission for six years and off chemotherapy for 2 1/2 years. One bone marrow sample showed marked leukemic infiltration, whereas marrow from another site was normal. Three months later, with normal peripheral blood counts, she developed severe back pain and x-ray evidence of vertebral collapse and periosteal changes in the public bone. At that time three of the four areas of bone marrow sampled showed leukemic involvement. Reinduction therapy was begun, and she is now in remission on maintenance chemotherapy. At this time, it is unclear whether routine performance of marrow aspirations and biopsies from multiple sites, in periodic follow-up examinations of patients with acute leukemia would allow earlier detection of relapse frequently enough to justify the procedure. The issue of localized bone marrow involvement, if more common than previously reported, should be addressed at the time a decision is being made to discontinue therapy.     

Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy

PURPOSE: Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults. METHODS: Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 +/- 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1-1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7-2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one. RESULTS: Hemodiafiltration was performed for 13 +/- 9 days. A high rate of clearance was achieved (52 +/- 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 +/- 9 days. Nine of the 10 children were successfully extubated; 8 survived. CONCLUSIONS: Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.     

Isolated testicular leukemia following bone marrow transplant for acute lymphocytic leukemia. The need for pretransplant testicular biopsies

Bone marrow transplantation has become an accepted mode of treatment for children with acute myelocytic leukemia in their first remission and acute lymphocytic leukemia after their first bone marrow relapse. Two-year survival rates of 50% can be achieved in patients undergoing transplant during remission, in contrast to a 2-year survival of 15% in those undergoing transplant while still in marrow relapse. Recurrence of bone marrow leukemia relapse is a significant cause of marrow transplant failure. Overt or occult testicular relapse occurs in 10-15% of males with acute lymphocytic leukemia receiving or having completed standard therapy regimens for control of their disease and frequently leads to a subsequent bone marrow relapse. This paper describes a child with acute lymphocytic leukemia who received a successful marrow transplant following bone marrow relapse and developed testicular leukemia relapse approximately 20 months after transplant. The experience with this child suggests that bilateral testicular biopsies should be a mandatory part of the routine evaluation to screen for residual leukemia before bone marrow transplantation.