Coeliac disease following high-dose chemotherapy

This report describes an interesting case of severe diarrhoea following high-dose chemotherapy for non-Hodgkin's lymphoma. This caused significant morbidity and resolved on a gluten-free diet. Copyright 2002 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.     

复方丹参联合低分子右旋糖酐预防造血干细胞移植后肝静脉闭塞病

 目的　观察复方丹参联合低分子右旋糖酐注射液预防造血干细胞移植（HSCT）后肝静脉闭塞病（HVOD）的临床效果。方法　在HSCT预处理时开始用复方丹参注射液20 ml,1次／d,静脉滴注,低分子右旋糖酐注射液250 ml,2次／d,静脉滴注,同时用保护肝细胞类药物。当血小板数降至30×109／L时停用复方丹参与低分子右旋糖酐,不再应用。结果　85次HSCT使用复方丹参联合低分子右旋糖酐预防HVOD均无HVOD发生,用复方丹参加低分子右旋糖酐时未发生出血。结论　复方丹参联合低分子右旋糖酐预防HSCT后HVOD安全有效。     

去纤苷防治造血干细胞移植后肝静脉闭塞病的研究进展

肝静脉闭塞病(HVOD)是造血干细胞移植(HSCT)后的严重并发症之一,重度HVOD患者的死亡率可高达100％.去纤苷是一种具有抗血栓及促进纤溶作用的单链寡核苷酸混合物.近年来,多个临床研究结果说明去纤苷是预防和治疗HSCT后HVOD安全有效的药物.文章就去纤苷的作用机制及其在HSCT后HVOD的治疗及预防中的应用进行总结.     

Successful therapy of transplant-associated veno-occlusive disease with a combination of tissue plasminogen activator and defibrotide

A 36-year-old man underwent matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia. He developed severe hepatic veno-occlusive disease as an early post-transplant complication. Tissue plasminogen activator was initially felt to be contraindicated since the patient had concomitant pericarditis. Defibrotide was therefore commenced as treatment for veno-occlusive disease. The pericarditis improved but the veno-occlusive disease continued to worsen (peak bilirubin 353 μmol/I). Tissue plasminogen activator followed by a heparin infusion was therefore administered. However, he proceeded to develop haemorrhagic cardiac tamponade that required drainage. Thrombolysis was therefore discontinued and treatment with defibrotide resumed after an interval of 48 h. The veno-occlusive disease gradually resolved and defibrotide was discontinued once the bilirubin had plateaued. He was discharged home on day +52 post-transplant.     

Probable veno-occlusive disease after treatment with gemtuzumab ozogamicin in a patient with acute myeloid leukemia and a history of liver transplantation for familial hemochromatosis

A 69-yr-old male with a history of familial hemochromatosis and status after liver transplantation was found to have severe thrombocytopenia (platelet count of 8000/μL). He was also anemic and was diagnosed with acute myeloid leukemia (AML) after a bone marrow biopsy. He was started on gemtuzumab ozogamicin (Mylotarg?) and developed hepatic and multiorgan failure consistent with veno-occlusive disease within 2 wk. He did not have a history of hematopoietic stem cell transplantation, which is usually the case in AML patients who develop veno-occlusive disease of the liver after treatment with Mylotarg.     

Frequency of veno-occlusive disease of the liver in bone marrow transplantation with a modified busulfan/cyclophosphamide preparative regimen

Veno-occlusive disease (VOD) of the liver is a major complication of bone marrow transplantation (BMT). The overall frequency of VOD has ranged from 20 to 30%, with a mortality rate greater than 40%, as reported by centers utilizing cyclophosphamide (Cy) and total body irradiation (CyTBI) or various chemotherapeutic regimens, including the busulfan (Bu) (4 mg/kg for 4 days) and Cy (50 mg/kg for 4 days) (BuCy4) combination. Since 1986, Hahnemann University (HU) has primarily used the BuCy2 regimen, i.e., Bu (4 mg/kg for 4 days) followed by Cy (60 mg/kg for 2 days). We reviewed 74 consecutive patients who received either an autologous or allogeneic BMT for various malignancies from January 1986 through October 1988 to determine the frequency of VOD. Seven of 74 consecutive patients met clinical criteria for VOD, for a total frequency of 9.5%. Fifty-five patients were conditioned with various other regimens. Only 5 of the patients conditioned with BuCy2 developed VOD (9.1%). This is less than the 25% reported frequency of VOD in patients who received CyTBI (1,000 rads) and less than the 24% reported frequency of VOD in patients who received BuCy4. Only one of seven patients who developed VOD died from the disease. One patient died of sepsis after the VOD had almost completely resolved. The remaining five completely recovered. We conclude that the total Cy dose, and not Bu, is the major factor in the occurrence of VOD in Bu/Cy BMT preparative regimens, and the BuCy2 regimen reduces the frequency of VOD in autologous and allogeneic graft recipients when compared to CyTBI or the BuCy4 regimens.     

Progression of Parkinson's disease with impairment of vision under carboplatin /cyclophosphamide therapy for ovarian cancer

We report on a patient who experienced a progression of Parkinson's disease with impairment of vision under carboplatin/cyclophosphamide therapy for ovarian cancer. Received: 22 September 1997 / Accepted: 21 October 1997     

异基因造血干细胞移植后肝静脉闭塞病的防治效果分析

背景与目的:肝静脉闭塞病(veno-occlusive disease of the liver,VOD)是造血干细胞移植常见的并发症之一,重型VOD的病死率几乎达100%,目前VOD的预防和治疗仍较困难。本研究总结具有发生VOD高危因素的造血干细胞移植患者的VOD预防和治疗方案,探讨更好的防治方法。方法:1999～2005年在中山大学附属第三医院用马利兰和环磷酰胺预处理的18例异基因造血干细胞移植患者,在移植前给予前列腺素E1、还原型谷胱甘肽、门冬氨酸鸟氨酸预防VOD,移植后发生VOD的患者予前列腺素E1、低分子肝素、组织型纤溶酶原激活物(tissue plasminogen activator,tPA)治疗。结果:18例患者中有11例移植后出现谷丙转氨酶水平升高,经治疗后降至正常;仅有1例发生VOD,为重型,经前列腺素E1和低分子肝素治疗效果不佳,予tPA治疗后完全缓解,副作用为皮肤粘膜出血。结论:针对VOD发病机制的多个方面,联合应用前列腺素E1、还原型谷胱甘肽、门冬氨酸鸟氨酸预防VOD,可能起到较好的预防作用,使用安全方便,值得进一步研究推广;在目前条件下对重型VOD,在严密观察下使用tPA可作为一个治疗选择。     

Veno-occlusive disease of the liver in children following chemotherapy for acute myelocytic leukemia

Three children developed acute veno-occlusive disease of the liver following combination chemotherapy for acute myelocytic leukemia. The clinical presentation was similar in all three, with acute onset of hepatomegaly and thrombocytopenia in the absence of significant transaminasemia or icterus. In all three patients, radionuclide imaging with technetium-99m sulfur colloid showed hepatosplenomegaly, decreased liver uptake, and increased splenic activity. The results of liver biopsy established the diagnosis, revealing marked centrilobular congestion with hemorrhage into the spaces of Disse, atrophy of central hepatic cords, and edema of the walls of the central and sublobular veins. Each patient showed marked improvement following temporary cessation of chemotherapy. The diagnosis of veno-occlusive disease is suggested by the triad of: (1) clinical signs and symptoms; (2) scintigraphic findings; and (3) temporal relationship to chemotherapy.     

Recent progress in the diagnosis and therapy for veno-occlusive disease of the liver

Veno-occlusive disease (VOD) is one of the severe complications of the liver, which may occur after hematopoietic stem cell transplantation (HSCT). Although an early diagnosis is important to initiate antithrombotic therapy before serious organ failure, the widely used clinical criteria only become clinically fulfilled at an advanced stage of disease. Liver biopsy provides useful findings for the diagnosis of VOD, however, in the later or less severe stages of VOD liver biopsy may provide false-negative sampling error because the biopsy sample may be too small to evaluate the whole liver. In addition it may be difficult to follow the clinical course with repeat biopsy in individual cases. Imaging diagnosis of VOD including gray-scale US, Doppler US, and MRI have been reported as convenient and useful. Color-Doppler US is superior because of its specificity and sensitivity. Blood sampling tests including factor VII, protein C, N-terminal propeptide for type III procollagen (P-III-P) and hyarulonic acid have predictive value, and their measurement may simply be another way to evaluate early hepatic impairment. Since no optimal treatment for VOD has been established as yet, the prophylaxis of VOD or early initiation of treatment is important. These new diagnostic approaches for VOD may provide a direction to resolve the clinical problems of VOD such as the time of initiation of therapy, the therapeutic regimen of choice, and the cessation of therapy.     

Addition of bortezomib to high-dose cyclophosphamide therapy as a conditioning regimen for autologous peripheral blood stem cell harvest leads to an increased yield of hematopoietic stem cells

Peripheral blood stem cell harvest (PBSCH) is a crucial procedure for autologous stem cell transplantation in patients with multiple myeloma. We herein report a retrospective study to verify the usefulness of bortezomib and high-dose cyclophosphamide therapy (Bor-HDCY) as a conditioning regimen for PBSCH. Thirty-three patients were evaluated. The median age at the first apheresis was 61 (interquartile range, 53–64) years old, and 18 (54.5%) patients were male. Bor-HDCY was performed in 15 patients, and HDCY was performed in 18. In the patients who underwent Bor-HDCY, the CD34⁺ cell count at the first apheresis was significantly higher than in the others (P<0.01), and the total CD34⁺ cell count also tended to be high (P=0.0933). In terms of apheresis days, two-thirds of the patients who underwent HDCY had two-day apheresis, whereas most who underwent Bor-HDCY had one-day apheresis. According to univariate analysis, Bor-HDCY (P<0.01), VRd (Bor, lenalidomide, and dexamethasone) as induction therapy (P=0.0529), and ≥VGPR before PBSCH (P=0.0767) were factors associated with a higher CD34⁺ cell count at first apheresis. Although multivariate analysis showed that there were no independently significant factors influencing the CD34⁺ cell count at the first apheresis, the stepwise selection method revealed that only the Bor-HDCY regimen remained in the final model (P<0.005). Bor-HDCY may be a useful conditioning regimen for increasing the CD34⁺ cell yield.     

Treatment of multicentric Castleman's disease complicated by the development of non-Hodgkin's lymphoma with high-dose chemotherapy and autologous peripheral stem-cell support

Background: Castleman's disease or angiofollicular lymph node hyperplasia is a rare entity with a localized/unicentric or a generalized/multicentric presentation. Whilie surgery is curable for most localized presentations, there is limited information regarding the optimal management of the multicentric type. The latter type is associated with a poor prognoses and can be associated with the development of lymphoma and infections.Patients and methods: In this report we describe a case of multicentric Castleman's disease who failed steroids and chemotherapy and developed a follicular mixed lymphoma. He was treated with high-dose chemotherapy with autologous stem-cell support and remains disease at four years of follow-up.Conclusions: A long-term durable remission may be possible with high dose chemotherapy with stem-cell support. This treatment modality should be considered an option in the management of multicentric Castleman's disease.     

Mitoxantrone, 5-fluorouracil and high-dose leucovorin (NFL) in the treatment of metastatic breast cancer: randomized comparison to cyclophosphamide,methotrexate and 5-fluorouracil (CMF) and attempts to improve efficacy by adding paclitaxel

The combination of mitoxantrone (12 mg/m² i.v., day 1) 5-fluorouracil (350 mg/m² i.v. days 1–3) and leucovorin (300 mg i.v. days 1–3) is an active and well-tolerated regimen for metastatic breast cancer. We compared this regimen to a standard CMF regimen (cyclophosphamide 600 mg/m² i.v. day 1; methotrexate 40 mg/m² day 1; 5FU 600 mg/m² i.v. day I) in a randomized, phase II study. One hundred and twenty-eight women receiving first-line chemotherapy for metastatic breast cancer were treated. NFL produced lugher response rates (45% vs. 26%) and longer remissions (9 months vs. 6 months) than did CMF; overall survival was not different (19 months vs. 16 months). Both regimens were well tolerated. In an attempt to improve efficacy, we added paclitaxel(l35 mg/m² i.v. 1-h infusion) to the NFL regimen. Although this regimen was active (51 % response rate in first-second-line treatment], myelosuppression was greater than expected. These results confirm the utility of NFL as an active, well-tolerated regimen for the palliative treatment of metastatic breast cancer.     

Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide,BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature

Four patients with limited disease small cell carcinoma of the lung were treated with high-dose cyclophosphamide (120 mg/kg over days 1 and 2), BCNU (400 mg/m² over days 1 and 2) and VP-16 (200 mg days 1–5) used as intensification treatment after conventional chemotherapy. To ameliorate hematopoietic toxicity, autologous bone marrow cells collected and cryopreserved prior to treatment were reinfused on day 8. In three patients clinical response was evaluable. Two achieved a complete remission: one died without evidence of tumor after 3 months; the other had a regional relapse after 6 months. One patient who had progression of disease on conventional chemotherapy was refractory to high-dose treatment. Three patients developed diffuse interstitial pneumonitis 3 weeks after treatment and two died of respiratory failure. High-dose intensification chemotherapy with autologous marrow reinfusion may complement the effects of standard combination chemotherapy in small cell carcinoma of the lung. The current status of this approach is reviewed.     

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide,thiotepa, carboplatin): the Netherlands Cancer Institute experience

High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m(-2), carboplatin 1600 mg m(-2) (or 20 mg ml(-1) min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m(-2) as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n=86) or metastatic (n=4) breast cancer, or a germ cell tumour (n=8). Two patients (with a medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the median time to neutrophil count 500 x 10(6) l(-1) and platelet count >20 x 10(9) l(-1) without transfusion independence was 10 (range 8-25) and 13 (8-60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic fever requiring antibiotics (n=65), central catheter-related infection (n=12) or a bleeding episode (n=48), mostly epistaxis (n=26). Reversible cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (infection (n=6), embolism (n=1)). Grade 3-4 gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28% and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with cisplatin had a kidney transplantation 8 years after HD-CT. Late complications included reversible radiation pneumonitis (n=12) and chronic heart failure (n=2). We found five second solid malignancies and two myelodysplasias. In conclusion, the CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.     

Extended preoperative chemotherapy,extent of liver resection and blood transfusion are predictive factors of liver failure following resection of colorectal liver metastasis

Aim

The aim of this study was to determine the incidence and prognostic factors of postoperative liver failure in patients submitted to liver resection for colorectal metastases.

Method

Patients with CLM who underwent hepatectomy from 1998 to 2009 were included in retrospective analysis. Postoperative liver failure was defined using either the 50–50 criteria or the peak of serum bilirubin level above 7 mg/dL independently.

Results

Two hundred and nine (209) procedures were performed in 170 patients. 120 surgeries were preceded by chemotherapy within six months. The overall morbidity rate was 53.1% and 90-day mortality was 2.3%. Postoperative liver failure occurred in 10% of all procedures, accounting for a mortality rate of 9.5% among this group of patients. In multivariate analysis, extent of liver resection, need of blood transfusion and more than eight preoperative chemotherapy cycles were independent prognostic factors of postoperative liver insufficiency. This complication was not related with the chemotherapy regimen used.

Conclusion

We conclude that postoperative liver failure has a relatively low incidence (10%) after CLM resection, but a remarkable impact on postoperative mortality rate. The amount of liver resected, the need of blood transfusion and extended preoperative chemotherapy are independent predictors of its occurrence and this knowledge can be used to prevent postoperative liver failure in a multidisciplinary approach.     

Index of pretreatment intensity predicts outcome of high-dose chemotherapy and autologous progenitor cell transplantation in chemosensitive relapse of Hodgkin's disease

Purpose: To identify prognostic factors in patients with chemosensitiverelapsed Hodgkin's disease treated by high-dose chemotherapy with autologousprogenitor cell transplantation (HDC) and to compare the duration oftreatment-free remission prior to HDC with the progression-free survivalafter HDC in individual patients.Patients and methods: Forty-five consecutive patients were analyzedretrospectively. We devised an index of pretreatment intensity (IPTI) basednumber of different chemo- and radiotherapy regimens given between diagnosisand HDC and on the duration of disease.Results: With a medianfollow-up of 47 months the post-transplant event-free survival (EFS) was44% and the overall survival (OAS) was 62% at four years. TheIPTI allowed to discriminate between a low and a high-risk group with afour-year post-transplant EFS of 66% and 11% and a OAS of87% and 28%, respectively (P = 0.0001). Of the 39 patientswith sufficient follow-up after HDC, post-transplant EFS lasted on 18.5months longer than the pretransplant treatment-free remission.Conclusions: HDC with the CBV regimen confers significant benefit topatients with chemosensitive relapsed Hodgkin's disease. The IPTI may help toselect patients with a good response to HDC and to identify poor prognosispatients suitable for experimental protocols or palliative care only.     

Salvage chemotherapy with high-dose leucovorin (LV) and 48-hour continuous infusion (CI) of 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) in patients with metastatic breast cancer (MBC) pretreated with anthracycline and taxanes

The purpose of this study was to evaluate the activity and tolerance of high-dose leucovorin (LV) and infusional 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) as salvage chemotherapy in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. 41 patients (median age 59 years) with MBC refractory or resistant to anthracyclines and taxanes were enrolled. The patients' performance status (WHO) was 0 in 10 patients (24%), 1 in 22 (54%), and 2 in 9 (22%). 30 (73%) patients had received 2 or more prior chemotherapy regimens. Cyclophosphamide (600 mg m(-2)) was given i.v. bolus on day 1 and LV (500 mg m(-2) d(-1)) as a 2-h infusion followed by 5-FU (1.5 g m(-2) d(-1)) over a 22 h c.i. for 2 consecutive days. Cyclophosphamide was administered every 28 days while 5-FU/LV every 14 days. In an intention-to-treat analysis, complete response (CR) was achieved in 2 (4.9%) patients and partial response (PR) in 9 (22%) (overall response rate 26.9%; 95% CI: 13.27-40.39%). Stable disease (SD) and progressive disease (PD) were observed in 9 (22%) and 21 (51%) patients, respectively. The overall response rate was 6% and 40% in patients with primary and secondary resistance to anthracyclines/taxanes, respectively (P = 0.047). The median duration of response and the median time to disease progression was 8 and 9.5 months, respectively. The median overall survival was 13 months and the probability for 1-year survival 51%. Grade 3/4 neutropenia occurred in 9 (22%) patients and 4 (9%) patients developed grade 3/4 thrombocytopenia. Non-haematological toxicity was mild. There were no cases of febrile neutropenia, toxic deaths or treatment-related hospital admissions due to toxicity. The combination of high-dose 5-FU/LV with conventional doses of cyclophosphamide is a well tolerated and effective salvage regimen in patients with MBC heavily pretreated with both anthracyclines and taxanes.     

Paget's disease of the breast: What the radiologist may expect to find

Paget's disease of the nipple is characterized by the presence of Paget's cells in the epidermis of the nipple or areola. Two case reports of Paget's disease are described and used to highlight unusual features of the disease. The literature on the radiographic and pathologic findings of this disease is reviewed.