Metastatic malignant melanoma presenting as pancytopenia in a three-year-old boy

Malignant melanoma is rare in childhood and has never been reported to cause pancytopenia due to bone marrow metastases in a child. We report a 3-year-old boy with a large congenital melanocytic nevus who presented with bone pain and pancytopenia due to diffuse bone and bone marrow infiltration with metastatic melanoma without an identifiable primary site. Despite treatment with imatinib mesylate there was no response and the patient died with progressive disease. This case illustrates an unusual presentation of bone marrow failure secondary to malignant melanoma in a young child with symptomatic metastatic marrow infiltration, a rarely reported site of melanoma involvement in adults or children.     

Hypocellular acute myeloid leukemia treated with bone marrow transplantation

Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11‐year‐old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo‐BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low‐dose cytarabine induced reduction of blasts, it did not lead to complete remission. He subsequently received myeloablative conditioning and allo‐BMT. Graft‐versus‐host disease (GVHD) prophylaxis included short‐course methotrexate and cyclosporine. Neutrophil engraftment (>5 × 10⁸/L) and platelet recovery (>10 × 10¹⁰/L) were achieved on days 13 and 27, respectively. He developed acute GVHD of the skin (grade 2), which responded well to treatment with prednisolone. He has remained in complete remission for 5 years since allo‐BMT. We consider allo‐BMT to be feasible for children with hypocellular AML.     

Haemophagocytic lymphohistiocytosis in children

OBJECTIVE: To evaluate the clinical and diagnostic features of children presenting with haemophagocytic lymphohistiocytosis (HLH), evolution of the disease and outcomes in response to treatment. METHODOLOGY: The medical records of 12 children, aged 5 weeks to 13 years at diagnosis, with HLH managed at a single institution were reviewed. RESULTS: Presenting features were fever, hepatosplenomegaly, pancytopenia and hypertriglyceridemia or hypofibrinogenemia. Nine patients (75%) developed central nervous system (CNS) disease. Only one child with CNS disease survived. Five children had complete responses to therapy (42%), but all relapsed at a median of 1.5 months after starting treatment (range 2 weeks to 5 months). Two of the children treated are long-term survivors (17%), both after allogeneic bone marrow transplantation. All deaths occurred in the context of active disease. CONCLUSIONS: Haemophagocytic lymphohistiocytosis is a disease with a poor prognosis. Central nervous system complications are common and response to treatment usually is transient. This study provides support for the use of immunomodulatory therapy for remission introduction followed by consideration of allogeneic bone marrow transplantation.     

骨髓活检塑料包埋在儿童低增生MDS-RC MD诊断中的意义

目的探讨骨髓活检塑料包埋法在儿童低增生MDS-RCMD临床诊断中的意义。方法应用骨髓活检塑料包埋技术,对长期未能确诊和有效治疗的全血细胞减少或两系减少患儿,进行骨髓病理学研究,并结合患儿的血象、骨髓细胞学以及临床疗效进行综合分析。结果通过应用骨髓活检塑料包埋技术,确诊了11例儿童低增生性MDS-RCMD,并及时进行了早期治疗。结论骨髓活检塑料包埋法是临床诊断儿童低增生MDS-RCMD非常重要的方法。     

小儿骨髓坏死19例

目的对19例小儿骨髓坏死（BMN）进行总结分析,探讨其临床和实验室特点。方法回顾性分析1996年1月~2005年11月住院治疗19例BMN的临床资料、实验室检查、治疗方法、随访资料,并进行总结。结果引起骨髓坏死的原发病15例为恶性疾病,4例为感染所致。贫血、白细胞减少和血小板减少是最常见实验室检查特点,骨髓涂片可见到典型坏死改变。结论恶性肿瘤是骨髓坏死主要原因,对于疑诊患者应及时行骨髓检查。     

Bone marrow examination before steroids in thrombocytopenic purpura or arthritis

Corticosteroids were used to treat two children with presumed idiopathic thrombocytopenic purpura and one with juvenile rheumatoid arthritis without examination of the bone marrow. Of the two with presumed idiopathic thrombocytopenic purpura, one had Fanconi's anaemia and the other may have had aplastic anaemia. The third child had acute lymphoblastic leukaemia. The diagnosis of Fanconi's anaemia was delayed. A diagnostic and therapeutic dilemma was caused in the second case. In the third, delayed diagnosis and, perhaps, compromised outlook resulted. These three cases re-emphasize the well aired caveats about the diagnosis of idiopathic thrombocytopenic purpura and juvenile rheumatoid arthritis and provide further support for the arguments of those who believe that if corticosteroids are to be used to treat such children, their bone marrow should be examined first.     

Value of Routine Bone Marrow Examination for Detection of Bone Marrow Relapse in Children with Standard Risk Acute Lymphoblastic Leukemia

The value of routine bone marrow examination (RBME) in children during and after treatment for standard risk acute lymphoblastic leukemia (SR-ALL) was Investigated. The clinical symptoms and peripheral blood findings at the time of bone marrow relapse of 28 children were reviewed and compared with those of 28 matched controls in continuous complete remission. Five (45%) children with bone marrow relapse during maintenance therapy and six (35%) after cessation of cytostatic treatment were asymptomatic at the time of relapse. Signs indicative of relapse duriny treatment were lymphoblast cells in the peripheral blood, thromhocytopenia, hepatomegaly, anemia, or leukopenia in decreasing order of frequency. Afer cessation of treatment these signs were lymphoblasts in the peripheral blood, hepatomegab, splenomegaly, thrombocytopenia, or leukocytosis. Except for one case with thrombocytopenia, no signs suspicious for relapse were found in the control groups. When each sign was evaluated separately only the presence of lymphoblasts in peripheral blood and hepatomegaly were significant symptoms for relapse after cessation of treatment. The mean percentage of lymphoblasts in the bone marrow at the time of relapse was significant& lower for patients with an unpredicted relapse (46.8%) than patients with clinical and/or laboratory evidence of relapse (79.5 %). When lymphoblasts were present in the peripheral blood the percentage of lymphoblasts in the bone marrow was always more than 40%, both during and after cessation of treatment. These data suggest a relation between clinical and laboratory symptom and progression of the disease. It is concluded that 467% of relapses are detected by RBME in the absence of clinical or laboratory symptoms. This early detection may have a positive prognostic influence with more effective treatment for relapsed ALL.     

骨髓细胞学检查在视网膜母细胞瘤中的应用价值

目的探讨骨髓细胞学检查在视网膜母细胞瘤转移中的应用价值。方法选取2008年1月至2009年4月临床确诊为视网膜母细胞瘤的211例患儿,在治疗前常规进行骨髓穿刺,并行骨髓细胞学检查,观察早期有无骨髓转移。结果在211例患儿中210例为正常骨髓象,1例骨髓中发现有肿瘤细胞,但不能确定是视网膜母细胞瘤肿瘤细胞。结论视网膜母细胞瘤早期骨髓转移发生率极低,入院患者是否应当常规做骨髓细胞学检查值得商榷。但骨髓细胞学检查仍然是早期发现转移的重要手段之一,对于存在高风险转移因素的患儿仍应积极进行此项检查。     

The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease

Background

Niemann–Pick disease type C (NPC) is a fatal, autosomal recessive lysosomal storage disease which may present in infancy with cholestatic jaundice and/or hepatosplenomegaly. In cholestatic patients with splenomegaly, a bone marrow aspirate has been advocated as a relatively accessible tissue to demonstrate storage phenomena. Typically in patients with NPC, macrophages with abnormal cholesterol storage, so called foam cells, can be detected in the bone marrow.

Aim

To review our experience of bone marrow aspiration in children with NPC presenting with infantile liver disease.

Methods

A retrospective analysis of 11 consecutive children (8 males) from Birmingham Children''s Hospital with NPC presenting with infantile liver disease was undertaken. The diagnosis of NPC was confirmed in all cases by demonstrating undetectable or low rates of cholesterol esterification and positive filipin staining for free cholesterol in cultured fibroblasts.

Results

The median age at presentation was 1.5 months (range 0.5–10). Bone marrow aspirates showed storage cells in only 7/11 cases. Bone marrow aspirates which had storage cells were undertaken at a median age of 11 months while those with no storage cells were undertaken at median age 2.3 months. The overall sensitivity of bone marrow aspirates for detecting storage cells in children presenting with infantile liver disease was 64%; however, for children who had bone marrow aspirates in the first year of life it was only 57%.

Conclusions

The sensitivity of bone marrow aspirate for the diagnosis of NPC disease in patients presenting with infantile liver disease was lower than previously reported. Where NPC is suspected clinically, definitive investigations should be undertaken promptly. There is a need to develop sensitive screening methods for NPC in children presenting with infantile liver disease.     

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.     

Hemogram and bone marrow morphology in children with chronic aplastic anemia and myelodysplastic syndrome

Background  Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both acquired disorders in which bone marrow fails to produce or release sufficient blood cells. Anemia, infections and thrombocytopenia are common signs of such diseases. Clinically, it is difficult to distinguish chronic aplastic anemia (CAA) from MDS, especially from MDS without splenomegaly. As prognosis and treatment of AA and MDS are different, it is extremely important to make a differential diagnosis for the two diseases. Methods  The medical records of 31 patients with CAA and 17 patients with MDS were retrospectively reviewed. Hemogram, bone marrow smear and biopsy for those patients were analyzed. Results  The mean counts of monocytes and platelets in the peripheral blood of the CAA patients were significantly lower than those of the MDS patients. Bone marrow smear showed a reduction of cellularity in CAA patients. The mean counts of myeloblasts+promyelocytes, myeloblasts+proerythroblasts, and megakaryocytes in the bone marrow of CAA patients were markedly lower than those in MDS patients. But the mean lymphocyte count was reversed. Bone marrow cells showed morphological abnormalities in MDS. Hematopoietic tissue in the bone marrow biopsy decreased obviously in more than 96% of the patients with CAA. Adipose tissue in the bone marrow of CAA patients increased obviously. A reduction or deficiency (<2 cell/piece) of megakaryocytes was noted in 28 patients with CAA. Fibrous tissue in the bone marrow was detected in 5 patients with CAA. Bone marrow biopsy results showed hypercellular changes in 12 MDS patients. Ten patients showed aggregated erythroblasts which were in the same stage of development, and 15 patients had abnormal localization of immature precursors (ALIP). Conclusions  Blood cell counts can be decreased in addition to the reduction of cellularity in the bone marrow without dyshematopoiesis in CAA patients. Peripheral blood monocytes, fibrous tissue and cellularity in bone marrow are increased in MDS. Dyshematopoiesis and ALIP may appear characteristically in the children with MDS. Histology of bone marrow is important in the differential diagnosis of MDS and CAA.     

Prevention of Gram-Positive Infections in Patients Treated with High-Dose Chemotherapy and Bone Marrow Transplantation: A Randomized Controlled Trial of Vancomycin

Between January 1986 and June 1988, 155 patients (73 children and 82 adults), who were candidates for bone marrow transplantation, were included in a randomized controlled trial (75 patients in vancomycin group and 80 patients in the group without vancomycin) to evaluate the efficiency of a short course of vancomycin (10 mg/kg IV every 6 hours, day -5 to + 1) in decreasing the incidence of Gram-positive infections during aplasia after high-dose chemotherapy and bone marrow transplantation. There was no statistical difference in the occurrence of documented septicemia, documented coccus Gram-positive infections, or fever of unknown origins during aplasia in the 2 groups. Thus, short prophylactic treatment with vancomycin proved inefficient in reducing morbidity due to infection after high-dose chemotherapy and bone marrow transplantation.     

Detection of Minimal Disease in Bone Marrow of Neuroblastoma Patients by Immunofluorescence

Indirect immunofluorescence studies were compared with conventional smear cytology in 82 paired bone marrow samples from children with neuroblastoma using monoclonal antibodies (MAbs) BW 575 (neuroblastoma-associated 95 kD glycoprotein) and BW 625 (ganglioside GD₂) and tetanus toxin labeling. Congruent results were obtained in 70 of 82, or 85% (positive/positive; negative/negative). In 12 of 82 (15%) patients, bone marrow infiltration was demonstrated by immunofluorescence but not by conventional cytology. As few as 0.01% neuroblastoma cells were reliably detected—in some cases even fewer. Because of antigen heterogeneity, false negative results were obtained in five cases with MAb BW 625, in two cases with MAb BW 575, and in no case with tetanus toxin. No antibodies showed any cross-reactivity to hematopoietic cells in either bone marrow of infants or during regeneration after chemotherapy. We conclude that this panel of antibodies is highly sensitive and specific to detect minimal disease in bone marrow of neuroblastoma patients, which has major implications for the staging procedure, monitoring treatment, early detection of relapse, and assessment of bone marrow status before autologous bone marrow transplantation.     

More aggressive bone marrow screening in retinoblastoma patients is not indicated: the memorial Sloan-Kettering cancer center experience

BACKGROUND: Bone marrow involvement in retinoblastoma patients is rare in the more industrialized nations. The purpose of the current study was to determine the frequency of bone marrow involvement in our series of retinoblastoma patients and to investigate whether the use of four bone marrow aspirates (BMA) and two bone marrow biopsies (BMB) has greater sensitivity for the detection of metastatic disease compared to what has been previously reported. METHODS: Retrospective analysis of the charts of 54 patients with retinoblastoma was performed. We performed 265 BMA, 134 BMB (4 aspirates and 2 biopsies per evaluation), and 67 lumbar punctures (LPs) in 54 patients with retinoblastoma. RESULTS: There were no patients found with bone marrow or cerebrospinal fluid (CSF) involvement at the time of the initial diagnosis. Although no patient died of distant metastases, two patients developed metastatic disease at recurrence, involving the bone marrow and other sites. For these two patients all four aspirates and two biopsies were positive for disease at the time of recurrence. CONCLUSIONS: Despite the use of four BMA and two BMB (as opposed to one bone marrow aspirate that is routinely performed in other centers), the detection of patients with metastatic disease was similar to what has been previously reported. Based on these data more aggressive evaluation of the bone marrow in retinoblastoma patients with clinically limited disease using four aspirates and two biopsies cannot be supported.     

Bone Marrow Necrosis Associated with Medulloblastoma

A 9-year-old Japanese boy with bone marrow necrosis associated with metastatic medulloblastoma is reported. The diagnosis of bone marrow necrosis was obtained nine months after operative removal of the medulloblastoma. Bone marrow necrosis was treated with a combination chemotherapy, but unfortunately he died of disseminated metastasis of medulloblastoma. This case suggests that the prognosis of bone marrow necrosis would be attributable to the behavior of the original tumor.     

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.     

Isolated bone relapse in a child with acute lymphoblastic leukemia off-therapy

Osseous relapse, as distinct from bone marrow relapse, is possible during treatment of childhood leukemia. The authors have observed an isolated leukemic bone lesion in an 8-year-old boy in complete bone marrow remission after a second full course of chemotherapy for a testicular leukemic localization. The radiological signs in our case are peculiar because a small bone of the foot (right talus) showed an increased density instead of rarefaction; histological examination demonstrated leukemic bone infiltration. Local radiotherapy (2400 cGy) was given and multidmg induction and maintenance for one year. Two years after the histological diagnosis the child is still in complete remission. This observation suggests that structural bone may be a sancturay site for leukemic cells.     

Bone marrow fibrosis and radiological changes of the long bones in children with acute megakaryocytic leukaemia

The diagnosis of acute megakaryocytic leukaemia (AMkL) may be difficult to establish owing to difficulties in obtaining adequate bone marrow aspirates secondary to bone marrow fibrosis. We describe three children without Down's syndrome under 2 y of age with AMkL. Although none of the patients had the non-random t (1;22) (p13;q13) translocation, bone marrow cells from all patients exhibited chromosome abnormalities with complex karyotypes, including trisomy 21 in two cases. All patients had profound bone marrow fibrosis and characteristic lamellar diaphyseal radiological changes of the long bones.     

BONE MARROW FINDINGS IN JUVENILE IDIOPATHIC ARTHRITIS

The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to heterogeneous clinical presentation and lack of specific laboratory tests. The authors investigated bone marrow of 25 untreated children with JIA at the onset of the disease. Bone marrow smears were evaluated for cell populations as well as myelodysplastic features and compared to two control groups. The characteristic of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count. There was no difference between JIA patients and control groups in terms of myelodysplastic features. These findings can be helpful in explaining hematological alterations in JIA.     

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48+-125+ months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.