A case of true malignant histiocytosis: identification of histiocytic origin with use of immunohistochemical and immunocytogenetic methods

We report here an autopsy case of true malignant histiocytosis. The patient was a 67-year-old woman who exhibited fever, wasting, hepatosplenomegaly, and progressive pancytopenia. The bone marrow aspiration disclosed hemophagocytosing cells, which resembled histiocytes. The molecular analysis did not show the clonal gene rearrangement of T-cell receptor or immunoglobulin heavy chain. Although the patient had been started on methylprednisolone pulse therapy and chemotherapy with etoposide, she died from cerebral hemorrhage. The autopsy specimens of spleen and liver showed extensive infiltration of atypical cells, for which histiocytic origin was identified with an immunohistochemical method using monoclonal antibodies against CD11c, CD68, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, lysozyme, antitrypsin and alpha1-antichymotrypsin. Recent investigations have disclosed that in most cases diagnosed as malignant histiocytosis, hemophagocytosis was reactive and not evoked by histiocytic malignancy. True malignant histiocytosis, for which histiocytic origin is confirmed, is extremely rare.     

急性白血病患者血小板无效输注的原因分析

目的：探讨急性白血病（AL）血小板输注无效的原因。方法：观察106例AL患者的263例次单采血小板输注效果并检测血小板抗体,分析讨论血小板无效输注的影响因素。结果：①AL血小板无效输注率为43．35％;②血小板抗体阳性检出率为32．32％;③血小板输注有效组与无效组的抗体阳性检出率的差异有统计学意义（P〈0．01）。④AL发热组输注无效率高于未发热组（P〈0．01）;脾脏肿大与无肿大组无效输注率差异有统计学意义（P〈0．01）。结论：引起血小板输注无效的病因复杂。血小板输注前应进行血小板抗体的筛选,避免或减少造成血小板输注无效的原因,提高血小板输注的有效率。     

Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia]

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.     

血液光量子疗法对急性白血病患者血小板输注效果的影响

目的　探讨血液光量子疗法对急性白血病患者血小板输注效果的影响。方法　将 5 4例血小板减少的急性白血病患者随机分为两组 ,治疗组采用血液光量子疗法行血小板输注 ,对照组单纯行血小板输注。两组均采用酶联免疫吸附法 ,在血小板输注前后定量测定血小板表面相关抗体 (PAIg G和 PAIg M) ;计数血小板 ,计算1、2 4小时血小板增值 (CCI) ;观察其临床效果和非溶血性输血反应 (NHFTR)。结果　血小板输注前两组 PAIg M及 PAIg G值无显著性差异 ,输注后两组 PAIg M无显著性差异 ,而治疗组 PAIg G值明显低于对照组 (P<0 .0 5 )。两组 1小时 CCI无显著性差异 ,治疗组 2 4小时 CCI和临床效果明显优于对照组 (P<0 .0 5 ) ;治疗组的 NHFTR低于对照组 (P<0 .0 5 ) ,其临床效果优于对照组 (P<0 .0 5 )。结论　血液光量子疗法可减少血小板输注无效     

Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin.

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.     

Vancomycin-dependent antibodies associated with thrombocytopenia and refractoriness to platelet transfusion in patients with leukemia

Two patients with leukemia experienced profound thrombocytopenia and refractoriness to platelet transfusion during vancomycin treatment. In one patient, withdrawal of drug and administration of platelet transfusions restored platelet counts to near normal levels (approximately 100 x 10(9)/L), however, subsequent challenge with vancomycin due to recurring infection again precipitated severe thrombocytopenia (platelets less than 10 x 10(9)/L) and life-threatening hemorrhagic symptoms. Potent vancomycin-dependent antiplatelet antibodies were detected in the serum of both patients during the refractory period using staphylococcal protein A rosette formation. Employing a monoclonal antibody-antigen capture enzyme-linked immunosorbent assay (ELISA), the patients were found to have vancomycin-dependent IgG antibodies that bound specifically to platelet glycoproteins (GP) IIb and/or IIIa. One of these antibodies failed to react with platelets deficient in GPIIb/IIIa obtained from an individual with Glanzmann's thrombasthenia. These findings provide the first major evidence for drug-dependent antibodies in association with severe thrombocytopenia and refractoriness to platelet transfusion in alloimmunized leukemia patients and, further, provide the first demonstration of vancomycin-dependent antibodies reactive with platelets.     

Platelet transfusion therapy in acute leukemia: lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty-nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.     

Platelet transfusion reaction associated with interdonor HLA incompatibility

An HLA-compatible platelet transfusion was followed by chills, fever, and severe respiratory distress in a multitransfused patient with chronic lymphocytic leukemia. During the previous 7 days the patient had received blood products without incident, including 8 units of red blood cells (RBC), 24 units of pooled random donor platelet concentrates, and five HLA-compatible platelet pheresis products. The patient had no demonstrable RBC, HLA lymphocytotoxic, platelet or granulocyte antibodies. The platelet donor, a multiparous female, had no granulocyte or RBC antibodies but had lymphocytotoxic antibodies against HLA-A2 CREG (cross-reacting group A2, A28, A23, A24) which reacted not with lymphocytes of the patient but with lymphocytes of the donor whose RBC were transfused 24 h prior to the platelet transfusion reaction and whose HLA type is A23, A24; B44, B57. No RBC donors had HLA lymphocytotoxic, granulocyte, or platelet antibodies against the platelet donor. The patient received three subsequent platelet transfusions from the same donor after removal of the antibody-laden plasma with no adverse reaction. These data suggest an interdonor reaction caused by the presence of cells from the RBC donor received by the patient 24 h prior to the transfusion of donor lymphocytotoxic antibody to HLA-A2 CREG antigens.     

Malignant histiocytosis resistant to anthracycline. Response to intensive treatment with etoposide and amsacrine

A 36-year-old woman, presenting with fever, pancytopenia, hepatosplenomegaly, and striking effacement of the bone marrow by true malignant histiocytes, was found to have no benefit from the systemic administration of cyclophosphamide, vincristine sulfate, doxorubicin, prednisone, and high-dose methotrexate with calcium leucovorin rescue. Striking histologic and clinical improvement was noted after the administration of two cycles of etoposide and amsacrine, each cycle consisting of 100 mg/sq m/day of each agent for five days. We believe that this therapy should be considered for future patients demonstrating aggressive presentations of malignant histiocytosis.     

Successful use of etoposide in an elderly patient with chronic recurrent hemophagocytic syndrome]

A 66-year-old man was admitted to our hospital for fever on January 19, 1998. He began showing periodic high fever in June 1997 and an increased serum LDH in August 1997. His history included surgery for esophageal cancer in 1993. On admission, the patient's body temperature was 38.5 degrees C. Physical examination was negative for lymphadenopathy, hepatosplenomegaly, and skin rash. Peripheral blood revealed a hemoglobin level of 8.6 g/dl and a platelet count of 7.9 x 10(4)/microliter. Bone marrow examination showed hypocellularity with marked histiocytic hemophagocytosis. The various bacterial cultures were negative. Serum LDH was elevated to 1,606 IU/l, and ferritin was greater than 3,000 ng/ml. Antinuclear antibodies were negative. No significant elevation of viral antibody titers including that to Epstein-Barr virus was found. Hemophagocytic syndrome (HPS) was diagnosed, but no underlying diseases was identified. The patient's condition was complicated by interstitial pneumonia and pleural effusion. gamma-globulin and pulse methylprednisolone both proved ineffective for the HPS; however, complete remission was achieved with cyclic intravenous administration of etoposide (VP-16, 150 mg/day). Interestingly, the interstitial pneumonia resolved promptly with etoposide therapy. The patient relapsed, in July 2001, exhibiting high fever, cytopenia, and marrow hemophagocytosis. His condition was ameliorated by administration of etoposide. This was a rare case of chronic and recurrent HPS of unknown etiology accompanied by interstitial pneumonia. Etoposide should be considered as a primary therapy for HPS and its complications in cases such as our patients.     

Unfurling the Rationale Use of Platelet Transfusion in Dengue Fever

Dengue fever and dengue haemorrhagic fever have emerged as a global public health problem in recent decades. The practice of platelet transfusion has been adapted into the standard clinical practice in management of hospitalized dengue patients. The exact indications and situations in which platelet have to be transfused may vary greatly. Blood components especially platelet concentrates due to their short shelf life are frequently in limited supply. Hence, appropriate use of blood is required to ensure the availability of blood for patients in whom it is really indicated, as well as to avoid unnecessary exposure of the patients to the risk of transfusion reactions and transmission of blood borne infection. The present study was conducted to evaluate the appropriateness of platelet transfusion done in dengue patients with thrombocytopenia. The present study was conducted on 343 serologically confirmed dengue patients admitted at JSS University Hospital between 1st January and 30th August 2009. Clinical data, platelet count and platelet requirements were analyzed. Among the 343 serologically confirmed cases, the prevalence of thrombocytopenia (platelet count < 100,000/cumm) was 64.72% (222 patients) and bleeding manifestations were recorded in 6.12% (21 patients). 71 (20.7%) patients of dengue cases received platelet transfusion. Among them 34 (47.89%) patients had a platelet count <20,000/cumm, 28 patients (39.44%) had platelet counts in the range of 21–40,000/cumm while the remaining 9 (12.67%) patients had platelet count between 41–100,000/cumm. Out of 37 patients with a platelet count >20,000/cumm 11 patients had haemorrhagic manifestations such as petechiae, gum bleeding, epistaxis etc., which necessitates the use of platelet transfusion. However, the remaining 26 patients with platelet count >20,000/cumm and with no haemorrhagic manifestations received inappropriate platelet transfusion. Transfusion of 36.62% of platelet concentrate was inappropriate. The study emphasizes the need for development of specific guidelines for transfusion of blood components, constant interaction and co-ordination amongst clinicians and transfusion centre for implementation of these guidelines and a regular medical audit to review the optimal utilization of blood components.     

Successful therapy of Ph1 positive chronic myelocytic leukemia with oral form of etoposide

A 33-year-old female was diagnosed as having chronic myelocytic leukemia (CML) with Philadelphia (Ph1) chromosome and breakpoint cluster region (bcr) rearrangement. Physical examination revealed a huge splenomegaly and laboratory data showed WBC 490 x 10(3)/microliter and NAP score 44. She was treated with hydroxyurea, alpha-interferon, or busulfan, but severe adverse reaction such as skin rash, fever, and arthralgia, which allowed the therapy discontinue was occurred. When the patient was treated with the oral form of etoposide, a semisynthetic podophillotoxin, the number of leukocyte has been successfully maintained less than 10 x 10(3)/microliters at the dose of 50-100 mg/day and splenomegaly completely disappeared. Although Ph1 chromosome was unchanged in the percentage after the therapy for 5 months, etoposide may be effective agent for a chronic or accelerated phase of CML. Alopecia which was reversible and well tolerable was the only side effect of the drug.     

Acute myeloid leukemia invasion of the central nervous system, detected only along the Virchow Robin space

A 66year-old man with sustained fever was diagnosed as having acute myeloid leukemia with multilineage dysplasia. Induction therapy with etoposide and AraC was initiated, but was ineffective. Although fever had persisted for more than a few days, there was no evidence of any infection on radiological examination or culture studies. The patient was disorientated and demonstrated personality change. After a severe convulsive seizure, the patient died. Autopsy findings showed that the leukemic cells had permeated the Virchow Robin space, but without a mass lesion in the cerebral parenchyma. He was diagnosed as having had central nervous system leukemia (CNSL) that provoked sustained fever, consciousness disturbance and convulsive seizure. These findings suggested that the Virchow Robin space plays a particular role in the development of CNSL. Even with repeated cerebrospinal fluid examinations and radiological tests, we were unable to correctly diagnose CNSL before death, which may indicate the intractability of diagnosing CNSL spread along the Virchow Robin space. This case provides useful information about the pathophysiology and diagnosis of CNSL.     

Transfusion requirements in patients with dengue hemorrhagic fever

Dengue viruses are endemic in Thailand and Southeast Asian countries. A retrospective study of 175 patients with dengue virus infection admitted at the Department of Pediatrics, Ramathibodi Hospital in 1997 was carried out. Fifteen and 160 patients were clinically diagnosed with dengue fever and dengue hemorrhagic fever (DHF), respectively. DHF was commonly found in patients whose ages ranged from 10 to 14 years. The mean body weight was at the 54th percentile for age. In the management, 10.6% of patients with DHF required blood component therapy which included platelet concentrate (64.7%) in patients who exhibited active bleeding, packed red cells (47%) in patients who exhibited a rapid drop in the hematocrit and fresh frozen plasma (29.4%) in patients with circulatory failure who did not respond to intravenous fluid. The transfusion requirement was significantly correlated with the occurrence of bleeding (p < 0.008) and bleeding in the gastrointestinal tract (p < 0.0001) but not correlated with the number of platelet counts (p = 0.207). As a result, physicians in charge should be aware of the transfusion requirement and communicate this to the blood bank in advance for the preparation of appropriate blood components.     

Long-term follow-up patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized

Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.     

Refractoriness to platelet transfusion in acute myeloid leukemia correlated with the optical density of anti-platelet factor 4/heparin antibodies

A small number of reports have described cases of heparin-induced thrombocytopenia complicating hematological disorders with impaired platelet production. We describe the case of a 66-year-old woman with acute myeloid leukemia who exhibited unexplained refractoriness to platelet transfusion, while receiving heparin flushes, and was found to have anti-platelet factor 4 (PF4)/heparin antibodies with high optical density (OD) values (>2 units) detected by an enzyme-linked immunosorbent assay. After cessation of heparin flushes, her refractoriness to platelet transfusion resolved. We retrospectively confirmed that the OD values for anti-PF4/heparin antibodies declined gradually; refractoriness to platelet transfusion resolved when the OD values fell below 1.0 units. Given the absence of any other evident explanation for this phenomenon, and the correlation between the OD values for anti-PF4/heparin antibodies and the efficacy of platelet transfusions, we conclude that the patient’s refractoriness to platelet transfusion was most likely caused by anti-PF4/heparin antibodies that had platelet-activating properties.     

Alloimmunization following prophylactic granulocyte transfusion.

Nineteen noninfected adults receiving initial induction chemotherapy for acute nonlymphocytic leukemia (ANLL) were randomized to receive either prophylactic granulocyte transfusion or platelet transfusion alone on an alternate-day schedule. An average of 11 granulocyte transfusions (range 3--19) were administered/patient with a mean dose of 11.5 X 10(9) granulocytes/transfusion. The groups were identical with respect to age, sex, number of days on study, granulocytopenic days, percent of days receiving systemic antibiotics, febrile days, complete remission rate, and incidence of minor infection. Significant transfusion reactions were much increased in the granulocyte transfusion group (7/10 versus 1/9 in controls) and were associated with the development of lymphocytotoxic antibodies (7/10 versus 4/9 controls), refractoriness to platelet transfusion, repeated fevers, and a pulmonary infiltrate in one patient. Alloimmunization to granulocytes occurred as early as the second week in some patients complicating platelet support during induction and maintenance. No severe infections occurred in the granulocyte transfusion group while three fungal infections occurred in the controls. The high rate of alloimmunization suggests that histocompatibility considerations indicate that prophylactic granulocyte transfusion should not be routine therapy and should be studied only in investigational settings.     

A restrictive platelet transfusion policy allowing long-term support of outpatients with severe aplastic anemia

The threshold for prophylactic platelet transfusions in patients with hypoplastic thrombopenia generally recommended in the standard literature is 20,000 platelets/microL. A more restrictive transfusion policy may be indicated in patients with chronic severe aplastic anemia (SAA) in need of long-term platelet support. We evaluated the feasibility and safety of a policy with low thresholds for prophylactic transfusions (相似文献   

Prevention and treatment of respiratory infections in leukemia patients

Among infections in leukemia patients during their first induction treatment pneumonia was the third most frequent infection (11.4%) following fever of unknown origin and sepsis. Granulocytopenia was suggested to be very closely related to the onset of pneumonia. Laminar air flow rooms seemed very effective for preventing exogenous infections including pneumonia. They reduced pneumonia from 30 to 0 in 106 patients with acute leukemia during their first induction treatment. Bone marrow transplantation (BMT) is one of the most intensive immunosuppressive treatments. Major causes of failure were interstitial pneumonitis (IP) due to cytomegalovirus (CMV), relapse of leukemia and bacterial and fungal infections. The incidence of IP was reduced by fractionation of total body irradiation and selection of CMV antibody negative donor for platelet transfusion. Administration of anti CMV immunoglobulin has also reduced the incidence of IP significantly from 37.5% to 11.5%. Colony stimulating factor appeared to stimulate the recovery of leukocytes after BMT. By several modifications of BMT techniques, mainly for the prevention of infection and IP, the survival of patients after BMT has improved significantly from 20% to 85%. In conclusion, prevention and treatment of respiratory infections are important in the treatment of leukemia, both for chemotherapy and BMT.     

肾综合征出血热患者血小板输注效果调查分析

目的:调查分析肾综合征出血热(HFRS)患者血小板输注效果。方法:根据血小板输注次数将70例116次输注血小板的HFRS患者分为3组,进行输注前及输注后24h外周血血小板计数,计算输注后血小板增加校正指数(CCI),进行血小板输注效果评价。结果:3组患者输注有效率比较差异有统计学意义(P0.05),以1次组有效率最高,其次为2次组,3次组有效率最低,平均有效率为37.93%。结论:HFRS患者血小板输注效果较差,且输注有效率随输注次数的增加而下降。