Thrombocytosis Associated with Solid Tumors in Children

The association between thrombocytosis and malignant disease was first described by Levin and Conley in 1964¹ but its pathogenesis remains unknown. We have studied the platelet counts in 108 children with solid tumors presenting to this hospital over the last 5 years. Thrombocytosis was defined as a platelet count over 400 × 10⁹/L and was noted in 43 children (40%) at presentation; in the great majority of cases the thrombocytosis could not be ascribed to infection or hemorrhage. The platelet counts in relation to the six commonest diagnoses are shown in Figure 1. The association was particularly marked in the case of hepatic tumors, where 8 out of 10 patients had platelet counts at presentation above 400 × 10⁹/L with a mean of 647 ± 306 (SD) × 10⁹/L (range 294-1310). Thrombocytopenia (platelet count less than 150 × 10⁹/L) was noted in 5 children at presentation; 2 of these had morphological evidence of bone marrow infiltration.     

Autologous Rescue with Blood-Derived Stem Cells in a Child with Non-Hodckin'S Lymphoma

Autologous blood-derived stem cells were used for stem-cell rescue in a 5-year-old boy with chemotherapy-resistant B-Non-Hodgkin's lymphoma (B-NHL) involving bone marrow. The high dose chemoradiotherapy was carried out 5 months after initial diagnosis during partial remission. The preparative regimen consisted of 12 Gy fractionated, total-body irradiation (FTBI) before 60 mg/kg etoposide. There were 22.96 × 10⁴/kg body weight myeloid precursor cells, granulocyte-macrophage committed stem cells (CFU-GM) collected by intermittent blood flow separation with a Haemonetics 30^R in two cytaphereses and stored in liquid nitrogen. Also 11, 82 × 10⁴ CFU-GM/kg body weight were recovered and transfused after thawing. Rapid hematopoietic reconstitution ensued: Erythroid precursors were detected on day 9, 1 × 10⁹/L leucocytes were counted on day 11, and 0.5 × 10⁹/L granulocytes on day 13, respectively. The patient required 3 single-donor platelet transfusions, the last one on day 10. On day 17, 100 × 10⁹/L platelets were reached. A bone marrow aspirate on the same day showed good trilineage regeneration. The patient remained in complete remission 7 months after autografting with a normal stem cell content of the bone marrow and in the peripheral blood. On day 226, after stem cell infusion, a bone marrow relapse occurred.     

Which one is a risk factor for chemotherapy-induced febrile neutropenia in childhood solid tumors: early lymphopenia or monocytopenia?

Neutropenia is one of the undesirable effects of cancer chemotherapy, sometimes causing life-threatening events. The present study was conducted to identify the risk factors of neutropenia caused by chemotherapy. Between January 2001 and March 2004, a total of 77 children with 165 neutropenic attacks were enrolled in this study. Complete blood count was performed before chemotherapy and on days 1, 3, 5, 7, and 9 consecutively. The complete blood count results of the febrile neutropenia (FN) group were compared to those of the non-FN group. The incidence of FN was significantly higher in patients with ANC counts ≤0.5 × 10⁹/L on days 3, 5, and 7, lymphocyte counts ≤0.5 × 10⁹/L on days 7 and 9, ≤0.7 × 10⁹/L on days 5, 7, and 9, and with monocyte counts ≤0.15 × 10⁹/L on days 7 and 9, respectively. Further statistical analysis showed that lymphocyte count ≤0.7 × 10⁹/L on day 5, and monocyte count ≤0.15 × 10⁹/L on day 7 were independent risk factors for FN. The authors conclude that lymphocyte counts on the 5th day can be more a predictive factor than monocyte count.     

Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans''cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a disease with an unpredictable course and unpredictable reactivations. Since active disease may cause life-long sequelae, early detection of reactivation is important. The usefulness of erythrocyte sedimentation rate (ESR) and thrombocytosis as indicators of disease activity in patients with LCH were examined. The mean values for ESR and platelet count for each quarter of a year were compiled. The means of all the ESR estimates (n=76) during each quarter of a year with active disease was 21 mm h^-1, with intermediate disease activity 11 mm h^-1 and with resolution 7 mm h^-1. The corresponding platelet count estimates (n = 139) were 433 × 109 l^-1, 365 × 109 l^-1 and 304 × 109 l^-1, respectively. In conclusion, elevated ESR and platelet count may be clinically valuable indicators of disease activity in LCH.     

以缺血性脑卒中为主要表现的儿童获得性免疫缺陷综合征1例

对2019年1月苏州大学附属儿童医院重症医学科收治的1例以缺血性脑卒中为主要表现的获得性免疫缺陷综合征患儿的临床资料进行回顾性分析。患儿,男,6岁4个月,既往有血小板减少性紫癜和反复呼吸道感染病史。主诉"右侧肢体乏力10余天"。头颅磁共振成像提示双侧额顶叶较广泛异常信号伴左侧丘脑、外囊软化灶形成。血常规示白细胞4.88×10⁹/L,淋巴细胞比例0.291,淋巴细胞计数1.42×10⁹/L,血红蛋白99 g/L,血小板23×10⁹/L。淋巴细胞亚群:CD3⁺84.1%,CD3⁺CD4⁺0.2%,CD3⁺CD8⁺61.4%,CD4⁺/CD8⁺0,CD3-CD19⁺9.2%,CD3-CD₁₆₊₅₆⁺6.1%,CD₁₉⁺CD₂₃⁺5.8%。输血前检查:人类免疫缺陷病毒(HIV)(⁺),余阴性。患儿父母双方均为HIV感染患者。本病例提示神经系统受累症状在HIV感染中并不少见,且脑卒中是HIV感染患儿出现临床局灶性神经功能缺损的最常见原因。高危患儿出现其他神经受累表现或认知改变,须尽早完善头颅磁共振检查。     

Oral Megadose Methylprednisolone Versus Intravenous Immunoglobulin for Acute Childhood Idiopathic Thrombocytopenic Purpura

Twenty children with acute idiopathic thrombocytopenic purpura (ITP) were randomized to receive either oral megadose methylprednisolone (MDMP) or intravenous immunoglobulin G (IV IgG). Normal platelet counts (150 × 10⁹/l) were obtained in 6 patients of each group in 3 days and in 8 and 9 patients treated with oral MDMP and with IV IgG within 1 week, respectively. It is concluded that oral MDMP could easily be used for the early elevation of platelet counts, which is important for ITP treatment.     

Effect of Iron Treatment on Erythrocyte Parameters in Postnatal Anemia of the Pig

The development of postnatal anemia and the preventive and curative effect of iron supplementation were examined in 34 piglets from three litters of Norwegian Landrace pigs. A prostaglandin analog was given on day 111 or 112 of pregnancy, and the piglets were removed by caesarean section. Seventeen piglets were given 180 mg iron as colloidal ferridextran subcutaneously at birth (0 = day group); the remaining 17 were given the same amount on day 13 (13-day group). The piglets had access to a milk substitute from day 1 to day 7 and pelleted food for piglets after day 13. From about 4 weeks of age the piglets ate considerable amounts of pellets.

The red blood cell count (RBC) and hemoglobin concentration (Hb) at birth were 3.2 ± 0.4 (SD) × 10¹²/L and 80.4 ± 8.1 × 10¹² g/L, respectively. In both groups Hb, RBC, mean corpuscular volume (MCV), and particularly packed cell volume (PCV) decreased markedly the first day after birth. In the 13-day group there was a further decrease until treatment with iron on day 13. Injection with iron on day 13 led to a rapid increase in the abovementioned parameters, with statistically significant increases for Hb, PCV, and MCV four days after treatment. The calculated mass of hemoglobin was fairly constant until treatment in the 13-day group.

In the group given iron at birth the data obtained indicate that the amount of iron given is insufficient to sustain a production of normal-sized erythrocytes with a normal mean corpuscular hemoglobin concentration for more than approximately 21 days. Furthermore, the present study also indicates that MCV is a sensitive indicator of iron availability in piglets.     

Transfusion-associated fall in platelet count in very low birthweight infants

Abstract Thirty-three infants with a birthweight of less than 1500 g were investigated retrospectively for the incidence and aetiology of thrombocytopenia occurring during the first week of life. The platelet count fell below 100 × 10⁹/l in 16 infants (48%). There was a moderately strong inverse correlation between the platelet count at its nadir during the first week or the first value below 100 × 10⁹/l and the percentage of blood volume transfused prior to this ( r =−0.61; P < 0.0001). When the platelet count was expressed as a percentage of the initial count the correlation was −0.74 ( P < 0.0001). The results were not affected by the elimination of the 10 infants with clinical conditions regarded as a probable cause of thrombocytopenia. The fitted least-squares regression line suggests that a transfusion equal to 10% of the blood volume on average reduced the platelet count by 19 × 10⁹/l or by 7% in these very low birthweight infants during the first week of life.     

Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP)

Immune thrombocytopenic purpura (ITP) is a disorder for which management remains controversial. The ongoing goal is to define the minimal therapy required for children with acute ITP. A pilot study of short-course oral prednisone (4 mg⁻¹ kg⁻¹ d⁻¹ for 4 d with no tapering) was undertaken in 25 consecutive children with acute ITP and platelet counts under 20 × 10⁹ 1⁻¹. Of the 25 children, 22 responded to the prednisone therapy by achieving a platelet count higher than 20 × 10⁹ 1⁻¹ within 1 week of commencing treatment. This regimen was found to be safe, inexpensive and effective in increasing the platelet count of children to a haemostatically safe level.     

Early Discharge Of Pediatric Febrile Neutropenic Cancer Patients By Substitution Of Oral For Intravenous Antibiotics

In an open, prospective pilot study of pediatric cancer patients, 23 episodes of fever and neutropenia were treated with intravenous and then oral antibiotics. After 72 hours, patients were changed from intravenous to oral antibiotics if the following criteria were met: negative blood cultures, temperature 38.0°C or lower for 24 hours, absolute neutrophil count less than 0.5 × 10⁹/L, and absence of clinical sepsis. Three patients (13%) had recurrent fever. Intravenous antibiotics were reinstituted in two of these three patients, and oral antibiotics were continued in the third. Fever was believed to be related to relapsed leukemia in one of the three patients. No focus of infection was defined in the other two, and both had good clinical outcomes. The study suggests that this approach to therapy is feasible and can be safely used for selected patients who are anticipated to have a short duration of neutropenia.     

儿童急性髓系白血病伴骨髓增生异常相关改变临床特征及预后分析

目的 探讨儿童急性髓系白血病伴骨髓增生异常相关改变(AML-MRC)的临床特征及其预后.方法 收集2014年6月至2020年3月确诊14例儿童AML-MRC的临床资料,对其临床特征、实验室检查、预后结果 进行回顾性分析.结果 14例AML-MRC患儿中位发病年龄11岁(范围1～17岁),男9例,女5例,初诊中位白细胞计...     

Familial Essential Thrombocyteemia

We report three siblings (2 F, 1 M) aged 9, 12, and 15 years with a thrombocytosis, above 650 × 10⁹/l for at least 18 months and a leukocyte alkaline phosphatase score below 37. The diagnosis of essential thrombocythemia was based upon the exclusion of a reactive thrombocytosis or another myeloproliferative disease. Cytogenetic examination of marrow cells was normal.     

Antiphospholipids antibodies in a 12-month-old presenting with idiopathic thrombocytopenic purpura

A 12-month-old Caucasian female with a history of recurrent ear infections presented to the emergency room with petechiae, severe thrombocytopenia (4000/μL), and abnormally prolonged activated partial thromboplastin time. Further autoantibody investigation detected antinuclear antibodies, anti-double-stranded DNA, and antiphospholipid antibodies. Platelet count, in response to intravenous immunoglobulin infusion, increased to more than 100 × 10³ plt/μL. At 6-month follow-up, no positive autoantibodies were detected.     

Infant anaplastic lymphoma: case report and review of the literature

Anaplastic large cell lymphoma (ALCL) is a well-known entity, but there are no data on prognosis according to the age of the patient, especially in infants. A 2-month-old girl was admitted with a 2-week history of coughing, fever, and lymphadenopathy. Physical examination revealed mild respiratory distress, an erythematous macular rash on her trunk, massive cervical lymphadenopathy, splenomegaly, and very mild ascites. Chest radiograph showed bilateral pulmonary infiltrates, pleural effusion, and a mediastinal mass. CBC count showed WBC: 172,000/μL (PMN 40%, lymphocytes 47%, monocytes 3%); hemoglobin concentration: 8.7 g/dL; platelets: 390,000/μL. Cervical lymph node biopsy revealed anaplastic lymphoma with positive staining to ALK 1 and TIA 1. Immunophenotypic analysis of peripheral and bone marrow lymphoid cells showed an aberrant T-cell immunophenotype, including expression of CD3, CD45R0⁺, CD43⁺, and CD30⁺. Cytogenetic analysis performed on blood and bone marrow samples demontrated the translocation t(2;5) (p23;q35), and trisomy 47. After leucophoresis, the child received chemotherapy according to the ALCL-99-EICNHL protocol, and was started on corticosteroids and cyclophosphamide, which resulted in marked improvement. After the second course, WBC decreased to 6000/μL without tumor lysis syndrome, but the child developed bacterial and fungal disseminated infections and died of septic shock with multiorgan failure. This report is of a rare case of infant anaplastic lymphoma and excellent response to treatment. Unfortunately, she did succomb to overwhelming infection. More reports of similar cases may determine the cause and prognosis of such children, helping to tailor therapy according to the age of the child and other prognostic factors, especially bone marrow involvement.     

Myelodysplastic Syndrome with Partial Deletion of the Long Arm of Chromosome 5: First Report of a Case in a Child

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 × 10³/l with 3% atypical lymphocytes, and platelet count 17.7 × 10⁴/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases.
These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.     

Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura

Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 × 10⁹ 1⁻¹, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions I gkg⁻¹ (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30mgkg¹ (n = 20) on two consecutive days. After 72h, IVIG had induced greater platelet responses (mean PC 188 × 10⁹ versus 77 × 10⁹1⁻¹ 2p < 0.001) and raised the PC to a haemostatically safe level above 50 × 10⁹1⁻¹ more frequently (91 versus 50%, one-sided e×act p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 × 10⁹1⁻¹ had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP.     

Seriousness of severe acquired aplastic anemia in children. Apropos of 32 cases

Thirty-two cases of severe aplastic anemia in children less than 16 years of age, observed between 1967 and 1985 in the Rh?ne-Alpes area were studied retrospectively. A toxic cause was suspected in 7 cases, an hepatitis in 5 cases. Patients presented with 2 of the 3 following cytopenias during the 3 weeks following diagnosis: hemoglobin level below 100 g/l, reticulocyte count lower than 20 G/l, neutrophil polymorphonuclear leukocyte count below 0.5 G/l, platelet count lower than 20 G/l. Whatever the treatment, prognosis was poor: 6 surviving patients (18.7%). Nineteen patients did not undergo bone marrow transplantation: only 2 are surviving after 4 years, one after low dose corticosteroid therapy, the other after antilymphocyte globulins and androgen therapy; 10 of 17 deaths occurred in the first 4 months. Thirteen bone marrow transplantations from sibling donors, of which 10 HLA A, B DR identical and 3 haploidentical allowed for 8 prolonged takes but only 4 survivors of whom 2 lasted for more than 2 years.     

Cerebrospinal Fluid and Plasma Methotrexate Levels Following High-Dose Regimen Given as a 3-Hour Intravenous Infusion in Children with Nonhodgkin's Lymphoma

In the French non Hodgkin's lymphoma protocols, central nervous system prophylaxis is provided by high-dose methotrexate (HD-MTX), given as a 3-hour IV infusion of 3 g/m² MTX along with intrathecal MTX injection. The incidence of CNS relapse is less than 3%. We designed a study to evaluate the MTX transfer across the blood brain barrier in terms of cytotoxic concentrations, during these short-term infusions. Cerebrospinal fluid and plasma MTX levels were measured during 61 courses in 29 children with non Hodgkin's lymphoma; none of them had central nervous system disease. Samples were obtained either 4, 12, 18, or 24 hours after the start of HD-MTX IV infusion. A potentially cytotoxic MTX level (10^-6 M) was reached in all courses at 4 hours (median: 2.3 × 10^-6 M) and remained available in 8/16 courses at 12 hours (median: 1.0 × 10^-6 M) and in only 2/17 courses at 18 hours (median: 0.29 × 10^-6 M). Twenty-four hours after the start of HD-MTX IV infusion, CSF MTX level was always less than 10^-6 M. The plasma MTX levels were 260, 1.3, 1.0, and 1.7 × 10^-6 M at 4, 12, 18, and 24 hours, respectively. There was no correlation between plasma and CSF MTX levels. These data show that potentially cytotoxic MTX concentrations can be reached in CSF after a 3-hour IV infusion of 3 g/m² in every patient and remain available for at least 8 hours in half of them.     

A case of axillary kaposiform hemangioendothelioma resembles a soft tissue sarcoma

Kaposiform hemangioendothelioma is a rare, aggressive vascular proliferation in children that is clinically and histologically distinct from hemangioma of infancy. It is often complicated with Kasabach-Merritt syndrome. The authors describe a 2-month-old girl who developed a rapidly enlarging deep subcutaneous solid tumor in the left axilla. The tumor size was about 10x7 cm and there was no skin change over the mass. The results of laboratory tests were significant for a moderate anemia (7.0 g/dL) and a profound thrombocytopenia (3x10/L). The preoperative radiologic findings were suspicious for a soft tissue sarcoma with scapular erosion. Anemia and thrombocytopenia were corrected by preoperative corticosteroid therapy and blood component transfusion. The tumor was excised totally and the pathologic findings were consistent with Kaposiform hemangioendothelioma. Serial blood examinations showed that the hemoglobin and platelet count returned to the normal range after surgery.     

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目的探讨母亲供髓异基因造血干细胞移植(Allo-HSCT)治疗恶性复发非霍奇金淋巴瘤的疗效和供体造血干细胞来源问题。方法2004年1月,第一军医大学南方医院儿科与海军总医院儿科给1例8岁男性淋巴母细胞淋巴瘤(LBL)患儿移植了母亲来源的HLA不全相合、ABO血型不合的骨髓造血干细胞。预处理选用阿糖胞苷、足叶乙苷、环磷酰胺和全身照射。预防移植物抗宿主病(GVHD)采用兔抗人T-淋巴细胞免疫球蛋白、环孢菌素A、甲氨蝶呤和CD25单克隆抗体。移植有核细胞数8.92×108/kg,单个核细胞数为1.89×108/kg,CD34细胞数为1.37×106/kg,CD3细胞数为32.9×107/kg。结果粒细胞绝对数>0.5×109/L的天数是移植后15d(+15d),血小板>30×109/L的天数是+20d,+27d采用荧光原位杂交性染色体检测显示99%为供者型。+37d受者血型由O型转变为供者血型B型。患儿于+19d出现Ⅰ度急性GVHD,给予激素冲击后,口服小剂量维持治疗,渐消退,随访1年余,未发生慢性GVHD。结论母亲来源的骨髓造血干细胞移植对LBL有根治性治疗作用,而且在一定程度上解决造血干细胞来源问题。