Successful treatment of chronic idiopathic neutropenia using recombinant granulocyte colony-stimulating factor

Summary A patient with chronic idiopathic neutropenia, who had been suffering from repeated infections, was successfully treated with recombinant granulocyte stimulating factor (rhG-CSF). Subcutaneous injection of 30g/m² rhG-CSF every two days was sufficient to maintain the neutrophil count at approximately 1,000/l. The patient has lived without any evidence of infection for the last 10 months using that treatment. There were no side effect caused by rhG-CSF and antibodies against G-CSF were not detected in the patient's plasma.     

COP-BLAM regimen combined with granulocyte colony-stimulating factor and high-grade non-Hodgkin's lymphoma

Abstract: The clinical efficacy of COP-BLAM chemotherapy combined with human recombinant granulocyte colony-stimulating factor (G-CSF) was evaluated in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL). According to the method of Laurence et al., a modified COP-BLAM regimen was administered every 21 days. G-CSF was added when the granulocyte count fell below 1000 × 10⁹/l. Ninety-eight of 104 (94.2%) patients achieved a complete remission; the 4-year survival rate was 82.4% with a median duration of observation of 26 months. Survival was significantly longer in patients with low serum LDH levels, B-cell type or low CRP or in earlier clinical stages, than in patients with high serum LDH levels, T-cell type or higher CRP levels or in advanced clinical stages. The mean duration of administration of G-CSF was 5.4 days. Twelve patients developed infections during treatment. The adverse effects of G-CSF included interstitial pneumonia, bone pain and fever. Patients administered COP-BLAM combined with G-CSF achieved a high rate of remission and had a low incidence of infection. Nearly all the patients could be treated in 21-day cycles. The results suggest that G-CSF combined with COP-BLAM was effective in treating NHL, because the patients can tolerate a higher dose of the anticancer agents.     

Comparative Effectiveness of White Blood Cell Growth Factors on Neutropenia,Infection, and Survival in Older People with Non‐Hodgkin's Lymphoma Treated with Chemotherapy

OBJECTIVES: To determine the effect of colony‐stimulating factor (CSF) on incidence of febrile neutropenia, infection, and survival in older people with non‐Hodgkin's lymphoma (NHL) treated with chemotherapy. DESIGN: Retrospective cohort study. SETTING: The Surveillance, Epidemiology, and End Results–Medicare database. PARTICIPANTS: Thirteen thousand two hundred twenty‐three people diagnosed with NHL at age 65 and older (mean age 74.9, range 65–102) in 1992 to 2002 who received chemotherapy within 12 months of diagnosis. MEASUREMENTS: Primary prophylaxis was defined as CSF administered at the start of chemotherapy before febrile neutropenia or infection; secondary prophylaxis was defined as CSF use after febrile neutropenia or infection. RESULTS: Participants with five to nine administrations of primary prophylactic CSF had a 42% lower risk of febrile neutropenia (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.41–0.83), and participants with 10 or more administrations had a 48% lower risk (OR=0.52, 95% CI=0.36–0.76) after adjusting for age, stage, histology, and comorbidity. Results did not differ significantly after adjusting for propensity score of receiving CSF. There was no significant association between primary prophylactic CSF and overall survival, but secondary prophylactic CSF was significantly associated with better survival. Four to 10 administrations of secondary prophylactic CSF was associated with 9% lower mortality risk (hazard ratio (HR)=0.91, 95% CI=0.84–0.99), 11 to 23 administrations was associated with 23% lower mortality risk (HR=0.77, 95% CI=0.71–0.84) and 24 or more administrations was associated with 13% lower mortality risk (HR=0.87, 95% CI+0.79–0.95) than in participants not receiving CSF after neutropenia or infection. CONCLUSION: Primary prophylactic CSF was observed to be effective in reducing the incidence of neutropenia and infection. These findings substantiate the clinical guidelines for recommending prophylactic CSF in older people with NHL receiving chemotherapy.     

Splenectomy in patients with malignant non-Hodgkin's lymphoma

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.     

Anti-HCV and HCV-RNA prevalence and clinical correlations in cases with non-Hodgkin's lymphoma

Hepatitis C virus (HCV) is an RNA virus in the Flaviviridae family. It displays lymphotropism in addition to hepatotropism and extrahepatic manifestations are very well known. There are many studies showing an association between HCV infection and non-Hodgkin's lymphomas (NHL). In this study the evidence for HCV infection was studied in cases with NHL. To this end, anti-HCV antibody and HCV-RNA were screened in serum samples of cases with NHL using third-generation ELISA and RT-PCR. Anti-HCV antibody was studied in 223 patients and was found to be positive in 18 cases (8.1%). Anti-HCV antibody positivity was compared with our blood bank/blood donor population. There was an important increased risk of HCV infection--the common odds ratio was 34.56 and corrected odds ratio was 19.07. HCV-RNA was studied in 67 of 223 serum samples. HCV-RNA was found to be positive in 21 of 67 samples (31.3%). When compared with clinico-demographic parameters for anti-HCV and HCV-RNA, including age, nodal status, and grade (in evaluable cases), except age in cases with or without HCV-RNA, we did not find an important correlation with HCV status and clinical findings (P=0.155; 0.442; 0.288 for anti-HCV and 0.027; 0,558; 0.126, respectively). These results suggest that HCV infection may be an important risk factor for lymphomagenesis and HCV-RNA is more useful for the detection of HCV infection in these immunosuppressed cases. Simultaneous detection of anti-HCV and HCV-RNA will be more informative in this population.     

Intralobar pulmonary sequestration in a patient with non-Hodgkin's lymphoma: a cause of confusion

Pulmonary sequestration, a rare congenital pulmonary disorder, is characterized by nonfunctioning lung tissue that is separated from normal tracheobronchial tree. We present a 60-year-old woman with diffuse large cell non-Hodgkin's lymphoma. After 6 cycles of chemotherapy, paratracheal and aorticopulmonary lymphadenopathies had disappeared. However, the size of the pulmonary mass in the left lower lobe had persisted. Percutaneous fine-needle aspiration biopsy of the pulmonary mass was not diagnostic, so thoracotomy was applied. The lesion was defined as pulmonary sequestration, and basal segmentectomy was performed. After proper and sufficient chemotherapy, histopathological diagnosis of any persisting masses should be confirmed prior to overtreatment decision.     

Occult lymphoma cells prevalent in autologous marrow from non-Hodgkin's diffuse lymphoma

The most effective treatment for recurrent non-Hodgkin's lymphoma (NHL) appears to be a high-dose cytotoxic chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT). However, it has been suggested that the presence of occult lymphoma cells in harvested marrow may be responsible for a significant fraction of treatment failures after HDC/ABMT. The present study examined randomly accrued NHL patients, independent of their cytogenic grades, for the presence of cells bearing bcl-2/immunoglobulin heavy chain (IgH) gene rearrangements in lymph node (LN) biopsies and the bone marrow by polymerase chain reaction (PCR) and Southern blot hybridization combined with a classical culturing technique. Among 41 NHL patients examined, bcl-2/IgH translocations were evident in LN biopsies and marrow from each of 10 follicular lymphoma patients, but not in any samples from 31 newly diagnosed diffuse lymphoma patients. Marrow aspirates from several patients that were cultured using a one-week "triggering culture" followed by an extended period of conventional culture resulted in emergence of a monoclonal, IgH-rearranged, bcl-2-normal lymphoid cell population. Such outgrowth was specifically seen in cultures of diffuse lymphoma marrow (7 of 28 evaluable patients). Southern analysis for IgH rearrangement within LN biopsies and of cells cultured from marrow of individual diffuse lymphoma patients produced identical patterns, suggesting that the occult lymphoma cells present in harvested marrow were derived from the predominant lymphoma cell population represented within involved lymph nodes. The culture of histologically occult lymphoma from diagnostic marrow and analysis of the derived cells by Southern blot hybridization can be used to detect potentially aggressive lymphoma cells within harvested marrow, despite their lack of bcl-2 gene rearrangement.     

Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients

Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte-colony stimulating factor (G-CSF) affects the balance in the production of anti-inflammatory cytokines. We investigated the serum IL-12 p40 and IL-12 Mix (p40 and p70) production in 28 patients with B-cell lineage non-Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G-CSF administration and eight healthy volunteers. We found that serum levels of IL-12 p40 (191.2 +/- 150.0 pg/mL) and IL-12 Mix (277.4 +/- 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL-12 p40: 76.4 +/- 25.3 pg/mL, IL-12 Mix: 48.5 +/- 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL-12 p40 and IL-12 Mix levels in nine patients receiving chemotherapy with administration of G-CSF (CG group, n = 9) and without G-CSF (C group, n = 9). Serum IL-12 p40 and IL-12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G-CSF decreased serum IL-12 p40 and IL-12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long-term administration of G-CSF appears to influence the survival rate by reducing immunosuppressive IL-12 p40 production.     

粒细胞集落刺激因子在急性肺损伤发病机制中作用的初步 …

目的：探讨粒细胞集落刺激因子（Ｇ－ＣＳＦ）在急性肺损伤（ＡＬＩ）发病过程中的作用。方法通过大鼠腹腔内注射内毒素建立ＡＬＩ模型。建立３０只大鼠分为５组：正常对照组及内毒素注射后２ｈ、４ｈ、６ｈ、８ｈ４个时相组,采用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）的方法检测肺组织内Ｇ－ＣＳＦ ｍＲＮＡ表达水平及相关指标。结果内毒素腹腔注射２ｈ组肺内Ｇ－ＣＳＦ ｍＲＮＡ表达明显高于正常对照组,４ｈ组达到最高值,２ｈ组     

Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL)

Summary Our purpose was to evaluate the ability of re-combinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemo-therapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemo-therapy according to the BMFT protocol and received in addition r-metHuG-CSF (200g/m²/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/l at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/l) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/l) in G-CSF-treated patients compared with controls (1880/l). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemo-therapy could be given on time to 11/13 (85%) G-CSF pa-tients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.     

供者用粒细胞集落刺激因子单倍体骨髓移植的临床研究

目的探讨供者用粒细胞集落刺激因子(G-CSF)和受者联合应用多种免疫抑制剂治疗的单倍体骨髓移植在降低重症移植物抗宿主病(GVHD)和改善无病生存的疗效.方法单倍体骨髓移植治疗白血病13例(单倍体移植组),移植后结果和连续完成的13例白血病HLA匹配异基因移植 (相合移植组) 相比较,单倍体移植方法是供者应用G-CSF 250 μg/d,连用7 d后采髓, 受者GVHD预防除环孢素A(CSA)和甲氨蝶呤(MTX)外,在移植前4～1 d用抗胸腺细胞球蛋白(ATG) 5 mg*kg-1*d-1, 移植后7 d始加服霉酚酸酯(MMF).结果单倍体移植组植入物CD+34细胞中位数6.1×106/kg,是相合移植组输入CD+34细胞中位数2.5×106/kg的2倍多(P＜0.01),单倍体移植组和相合移植组植入物CD+3细胞中位数分别是50.5×106/kg和47.0×106/kg(P＞0.05).移植后无1例发生植入失败,两组造血重建速度无差异(P＞0.05),所有患者经骨髓植活直接证据检测证实为完全供者造血.单倍体移植组发生急性Ⅱ～Ⅳ GVHD 5例(38.5%),可评价的8例中7例发生慢性GVHD(87.5%),为局限性慢性GVHD,这与相合移植组差异无显著性 (P＞0.05).单倍体移植组中位随访453 d(180～690),移植相关死亡5例,无复发死亡病例,剩余8例无病存活(61.5%).相合移植组中位随访510 d(220～810),移植相关死亡2例,复发死亡2例,9例无病存活(69.2%),通过比较两组差异无显著性(P＞0.05).结论本研究单倍体骨髓移植治疗白血病是一种安全和有效方法,在降低重症急性GVHD 及改善无病生存方面和HLA相合同胞供者移植相当.     

预激疗法治疗难治性急性髓细胞白血病疗效分析

目的 :探讨预激疗法对难治急性髓细胞白血病 (AML)的临床疗效和毒副作用。方法 :选择 2 0 0 2年6月～ 2 0 0 4年 9月在我院治疗的难治性AML 36例 ,均为用经典方案诱导化疗 2个疗程未获完全缓解或首次完全缓解 6个月内复发或 6个月后复发经正规诱导化疗无效者。男 2 0例 ,女 16例 ,中位年龄 35 (18～ 5 6 )岁。 2 0例选择强烈化疗方案 ,主要方案有VP16 10 0mg/m2 (第 1～ 4天 )加Ara C 2g/m 2 q 12h(第 1～ 4天 ) ;MIT 10mg/m2 (第 1～ 3天 )加VP 16 10 0mg/m2 (第 1～ 5天 )Ara C 2 0 0mg/m 2 (第 1～ 7天 ) ;HHT 4mg/m 2 (第 1～ 7天 )加ACR 4 0mg/m2 (第 1～ 3天 )加Ara C 2 0 0mg/m2 (第 1～ 7天 )。 2 0例选用预激治疗 ,其中 4例是在强烈化疗失败后转为预激治疗 ,具体方案G CSF 2 0 0 μg/m2 (化疗前一天用 ,共计 14d)加Ara C 10mg/m2 q 12h(第 1～14d)加ACR 10～ 14mg/m2 (第 1～ 4 ,10～ 14天 )或HHT 1mg/m2 (第 1～ 14天 )。结果 :强烈化疗组 2 0例患者 ,经上述方案化疗后 ,完全缓解 12例 ,部分缓解 2例 ,无效 6例 ,部分缓解和无效的 8例患者因一般情况差未能行第 2疗程强烈化疗 ,其中 4例换用预激治疗 ,4例姑息治疗 ,评价完全缓解率 6 0 % (12 / 2 0 ) ,有效率 70 % (14 / 2 0 )。2 0例经预激治     

Castleman's disease and lymphoma: report of eight cases in HIV-negative patients and literature review

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder associated with a risk of developing malignant lymphoma. We have recorded 8 HIV-negative patients presenting this association, 6 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's disease (HD). After literature review, we analyzed all reported cases of association CD-NHL (n = 23) and CD-HD (n = 27). NHL is more often associated with multicentric CD, its diagnosis being concurrent with CD diagnosis or occurring within 2 years. B-NHL is predominant (71%), and mantle cell lymphoma represents 40% of these B-NHL cases. NHL displays an aggressive course and is liable for death, especially in multicentric CD. HD occurs in localized CD of plasma cell type, usually in the same areas, is more often of interfollicular subtype, and its clinical course seems better than NHL. The association of CD and lymphoma seems to be more than coincidental, and its pathogenesis is discussed.     

CD34+ dose-driven administration of granulocyte colony-stimulating factor after high-dose chemotherapy in lymphoma patients

Our goal was to optimize use of granulocyte colony-stimulating factor (G-CSF) after high-dose chemotherapy and autologous peripheral blood stem-cell transplantation in lymphoma patients, limiting G-CSF administration to patients infusing a suboptimal CD34(+) cell number. Of 124 consecutive patients with histologically proven Hodgkin's and non-Hodgkin's lymphoma from January 2001 to June 2004, 60 patients (group 1) given > or = 5 x 10(6)/kg CD34(+) cells received no G-CSF; 64 patients (group 2) given < or = 5 x 10(6)/kg CD34(+) cells received G-CSF from day +5 after stem-cell reinfusion. The median times to reach 0.5 x 10(9)/L and 1.0 x 10(9)/L neutrophils were, respectively, 3 and 4 d shorter in G-CSF group and this difference was statistically significant (P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G-CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G-CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34(+) cell dose.     

Detection of hepatitis C virus RNA in paraffin-embedded tissues from patients with non-Hodgkin's lymphoma

The aim of this study is to detect the possible role of hepatitis C Virus (HCV) in lymphomagenesis. HCV-RNA and anti-HCV antibodies were studied in tissue and serum samples taken from patients with non-Hodgkin's Lymphoma (NHL). The prevalence of HCV, the clinical presentation of these cases, and association with histologic subtypes were determined. RT-PCR was used to detect the HCV-RNA in serum and tissue samples. The anti-HCV antibodies were tested with microparticle enzyme immunoassay. Immunohistochemistry with the ABC method was used to detect the HCV core protein in HCV-RNA(+) cases. RNA could be detected in 30 of 35 cases, and other tests were performed in these 30 samples. HCV-RNA was detected in 11 tissue samples (11/30, 37%). HCV core protein was studied in 10 of 11 HCV-RNA(+) cases, and 1-3% nuclear staining was found in only 2 samples. Serologically, HCV-RNA was detected in 7 of 30 samples (23.3%) and anti-HCV antibody was detected in 3 of 30 samples (10%). Detection of HCV-RNA in 37% of the lymphoma tissue samples suggests that HCV may have a role or is a contributing factor in the pathogenesis of lymphoma. The very low HCV core protein in lymphoma tissues may be due to the low viral load in lymphoid tissues and/or higher sensitivity of the PCR method. Detection of anti-HCV antibody in only three cases may be associated with undetectable levels of antibodies due to the immune deficiency in cases with NHL.     

供者用粒细胞集落刺激因子后骨髓细胞成分的变化及移植后临床分析

目的了解供者应用粒细胞集落刺激因子(G-CSF)后骨髓细胞成分的改变及移植后促造血重建和减轻移植物抗宿主病(GVHD)的疗效.方法供者应用(研究组)和未用G-CSF(对照组)各12例进行异基因骨髓移植,研究组供者接受G-CSF(Lenograstim) 250 μg/d 连用7 d后采髓,比较研究组和对照组植入物造血成分CD+34、粒-单细胞集落形成单位(CFU-GM)、巨核细胞集落形成单位(CFU-MK)和CD+3及亚群的改变,及移植后对造血重建和急性GVHD的影响.结果两组在采集大致相同体积的骨髓植入物中,研究组采集的有核细胞数(TNC),CD+34,CFU-GM和CFU-MK明显高于对照组(P＜0.01),两组CD+3类同,CD+4减少,CD+8增加(P＞0.05),CD+4/CD+8明显减少(P＜0.01).研究组和对照组骨髓CD+34和T淋巴细胞亚群百分数及CFU-GM与CFU-MK增殖进行分析,显示类似变化的结果.研究组移植后中性粒细胞>0.5×109/L的时间是16 d(11～23),血小板>20×109/L的时间为17 d(14～25),对照组分别为20.5 d(14～29)和23.0 d(17～32)(P＜0.05).研究组无1例发生急性Ⅱ～Ⅳ GVHD,对照组3例发生急性Ⅱ～Ⅳ GVHD,两组比较差异无显著性(P＞0.05).结论异基因骨髓移植供者应用G-CSF 可促进造血恢复作用,这与增加植入物中CD+34、CFU-GM和CFU-MK数量有关,具有降低急性重度GVHD发生的倾向.