Aggressive angiofollicular lymph node hyperplasia (Castleman's disease) treated with high dose melphalan and autologous bone marrow transplantation

A case of aggressive widespread angiofollicular lymph node hyperplasia in a 42-year-old male, treated with high dose melphalan is presented. The disease had failed to enter a durable remission after chemotherapy. High dose melphalan with autologous bone marrow transplantation achieved a complete remission which has lasted for 15 months to date. This approach can be considered when other measures fail.     

2-Chloro-deoxyadenosine induces durable complete remission in Castleman's disease but may accelerate its transformation to non-Hodgkin's lymphoma

There is currently no consensus on the best treatment for unresectable hyaline-vascular variant or for multicentric Castleman's disease (MCD), because none of the reported regimens have consistently produced complete response or durable remission in the majority of patients. In the present study, we report on the use of 2-CdA (2-chloro-deoxyadenosine) in three patients, two of them with MCD and one with unresectable hyaline-vascular type disease. Relapse-free survival of the responding patients was 24 and 20 months. Later, both patients evolved to non-Hodgkin's lymphoma (NHL) (diffuse large B-cell lymphoma and peripheral T-cell NHL, respectively). 2-CdA typically causes a long-lasting state of immunodeficiency and the profound influence of this drug on the immune system has raised questions concerning the emergence of secondary neoplasms after its use. Therefore, it is reasonable to conclude that: 1) 2-CdA can induce durable complete remission in MCD patients but unfortunately it cannot cure the disease; 2) the possibility that 2-CdA may accelerate the transformation of MCD to NHL cannot be ruled out.     

经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

目的 观察经导管肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝细胞癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

A pilot phase II study of ofatumumab monotherapy for extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue (MALT) lymphoma

These are the final results of the Ofatumumab in MALT lymphoma study (O‐MA 1), a pilot phase II trial evaluating the capacity and safety of ofatumumab to induce objective responses in patients with Helicobacter pylori eradication refractory or extragastric MALT lymphoma. Ofatumumab was given at 4 weekly doses (1000 mg) followed by 4 doses at 2‐month intervals starting at week 8. According to protocol, a total of 16 patients were recruited (median age 69 years; range 38‐85). Thirty one percent (5/16) of patients had primary gastric MALT lymphoma while the remaining 69% (11/16) presented with extragastric manifestations. Seventy‐five percent (12/16) had localized lymphoma and 4 patients disseminated disease. The overall response rate to treatment with ofatumumab was 81% (13/16), with the median time to best response being 5.5 months. In detail, 50% (8/16) achieved complete remission; 31% (5/16), partial remission; and 19% (3/16), disease stabilization as best response. However, 1 patient with gastric lymphoma and complete remission at second restaging had a relapse at final assessment but ongoing complete remission during further follow‐up. Tolerability was excellent accept low‐grade infusion reactions occurring in 86% (14/16). At a median follow‐up time of 25 months only 1 patient has relapsed suggesting durable responses in the majority of patients. This pilot trial shows clearly that ofatumumab is active and safe for the treatment of MALT lymphoma.     

FPN1、DMT1在肝细胞癌中的表达及其与药物疗效的关系

目的 研究膜铁转运蛋白1（ferroportin 1,FPN1）和二价金属离子转运体1（divalent metal transporter 1,DMT1）在人肝细胞癌（hepatocellular carcinoma,HCC）癌组织中的表达及与临床病理特征、药物疗效的关系。方法 回顾性收集行肝癌切除术后复发转移并接受化疗或索拉非尼治疗的HCC患者的临床及病理资料。采用免疫组化法检测HCC癌组织中FPN1及DMT1的表达,分析其与HCC患者临床病理特征、药物疗效的关系。结果 27例HCC患者无完全缓解者,其中接受奥沙利铂联合替吉奥方案化疗16例,获部分缓解2例,疾病稳定2例,疾病控制率（DCR）为25.0%;接受索拉非尼治疗11例,部分缓解1例,疾病稳定 2例,疾病控制率为27.3%。全组患者中位PFS为5.4个月,中位OS为10.0个月。FPN1和DMT1在HCC癌组织中的阳性表达率分别为62.96% 和81.48%,FPN1及DMT1的表达与肿瘤分化程度相关（P＜0.05）,与其他临床病理特征无关（P＞0.05）。FPN1阳性患者的DCR为41.2%,中位PFS为6.7个月,中位OS为15.7个月,优于阴性患者的10.0%、1.8个月和8个月（P＜0.05）;DMT1 阳性患者的DCR为18.2%,中位PFS为3.2个月,中位OS为 9.3个月,低于阴性患者的60.0%、18.6个月和35.9个月（P＜0.05）。结论 FPN1和DMT1在HCC中的表达可能受癌细胞分化程度影响,与晚期HCC患者药物治疗后的远期生存有关。     

Repeated dearterialization of hepatic tumors with an implantable occluder

A new implantable device for repeated hepatic dearterialization was evaluated in 13 patients with tumors of the liver. Eleven patients had colorectal secondaries and also received cyclic intraperitoneal infusion of 5-fluorouracil. Two patients had primary hepatocellular cancer (HCC). Four patients had a variant arterial supply. The hepatic artery was occluded repeatedly for 1 hour twice daily for 1 to 17 months (mean, 8.5 months). A complete transient occlusion was obtained in all but three patients, in whom minor collaterals were missed at the initial operation. Collaterals developed in two patients during therapy. Leakage from the balloon occurred in two patients after 5 and 12 months. Two patients developed thrombosis of the hepatic artery during therapy due to the cuff being placed too tightly around the vessel. A complete remission was demonstrated in one patient with HCC, a partial response in three patients (one HCC and two metastatic), stable disease in two patients, and progression in five patients. Median survival for colorectal lesions was 15 months (range, 2 to 23 months) from start of the occlusions. Four of nine patients developed calcifications of their lesions during therapy. One patient with HCC was alive and free of disease 18 months after the start of the occlusions. Both patients with HCC had an obstructed portal vein which may have contributed to the favorable outcome. The occluder was uniformly accepted by the patients who were able to do their occlusions at home.     

Cisplatin-based chemotherapy in primary central nervous system germ cell tumors

We report a retrospective review of our experience with cisplatin-based chemotherapy in eight patients (ages 9–44 years) with histologically confirmed primary central nervous system germ cell tumors. Five patients received chemotherapy as the primary treatment, radiation therapy being administered either at completion of chemotherapy or between chemotherapy courses. Three patients received cisplatin-based chemotherapy for recurrent disease after prior radiation therapy and/or surgery. Four of five patients treated with chemotherapy at diagnosis are in complete remission at 11–14 months from diagnosis. The remaining patient twice achieved complete remission prior to dying of progressive disease 16 months after diagnosis. Two of three patients treated with chemotherapy for recurrent disease are in complete remission at 20 and 26 months; the remaining patient deteriorated after the first cycle of chemotherapy and expired six months thereafter. Overall, of seven patients evaluable for response, five achieved complete remission with chemotherapy alone, and two with chemotherapy and radiation therapy. Our results confirm previous reports of high complete remission rates utilizing cisplatin-based chemotherapy in conjunction with radiation therapy. Prospective evaluation of cisplatin-based chemotherapy followed by radiation therapy is warranted.     

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months (patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 micro g of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies.     

Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease

Thirty-six consecutive patients with advanced recurrent Hodgkin's disease resistant to chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) were treated with doxorubicin (Adriamycin), bleomycin, (dacarbazine) DTIC, (lomustine) CCNU, and prednisone (ABDIC). Among the 34 patients evaluable for response, complete remission occurred in 35% and partial remission in 35%. The achievement of complete remission during primary MOPP induction was a statistically significant prognostic factor that predicted complete remission with ABDIC (p less than 0.01). The median time to complete remission was 2 months (range 1-11 mo). The median relapse-free survival time for complete responders is 47 months, and an estimated 53% of all patients who achieve complete remission are projected to be alive, free of disease off therapy at 3 years from initiation of ABDIC. The median survival of all patients is 24 months. The median survival of complete responders, partial responders, and nonresponders is 70, 17, and 4 months, respectively. The survival curve for complete responders is significantly different from that for partial responders (p less than 0.01); the survival curve for partial responders is also significantly different from that of nonresponders (p less than 0.01). Toxicity of ABDIC was acceptable; only one patient died from complications of myelosuppression. Our results indicate that ABDIC is a potentially curative regimen for a fraction of patients with MOPP-resistant Hodgkin's disease who achieve complete remission with prior MOPP therapy. It also prolongs the survival of patients who do not achieve complete remission with prior MOPP therapy.     

Pentostatin induces durable remissions in hairy cell leukemia

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.     

Chemotherapy-induced Complete Regression of Choroidal Metastases and Subsequent Isolated Leptomeningeal Carcinomatosis in Advanced Breast Cancer: A Case Report and Literature Review

Choroidal metastases from breast cancer represent an unusual metastatic presentation that has been traditionally treated with radiation therapy.Herein, we report a case of metastatic breast cancer presenting with pulmonary, cutaneous, lymph node and symptomatic choroidal metastases treated with systemic combination chemotherapy incorporating docetaxel and mitoxantrone without induction or consolidation radiation therapy to control visual symptoms from choroidal metastases. The patient experienced a durable complete remission in all metastatic sites that was maintained for 21 months since the initiation of chemotherapy, afterwhich she developed isolated leptomeningeal carcinomatosis managed successfully with intensive intrathecal methotrexate and whole brain irradiation leading to a new complete remission maintained until this report; 11 months after its presentation. This is the first case to our knowledge reporting complete regression of choroidal metastases with docetaxel-based chemotherapy as the only treatment modality and subsequent isolated leptomeningeal carcinomatosis recurrence.     

Treatment of acute myeloid leukemias in the adult in relapse

Main chemotherapy regimens used to treat adult patients with acute myeloid leukemia (AML) in first or further relapse were reviewed. In retrospective study, second complete remission rates ranged from 30% to 64%, while they ranged from 8% to 89% in prospective trials. The second complete remission rates were closely associated with age and duration of first complete remission. Combination therapies resulted in higher complete remission rates but were associated with higher toxicity. Median duration of second complete remission was < 14 months and overall median survival was < 12 months. The probability of 3-year survival ranged from 8% to 29%. The inhomogeneity of these studies, the differences in dosages and schedules, and the frequent absence of randomisation make it difficult to select the best salvage therapy. No reinduction regimen has so far clearly proven superior. Only stem cell transplantation provided durable remissions for the majority of AML patients after a first relapse. Considering the poor outcomes of patients with AML in first relapse, improved therapies need to be developed. A number of novel agents that include several differentiation agents, enzyme inhibitors, and monoclonal antibodies have been studied to provide improved outcomes for patients with AML who have relapsed. This is the same for acute promyelocytic leukaemia (APL). Arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. Within this context autologous and allogeneic bone marrow transplantations are also considered in second or subsequent relapse. Molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse ultimately improving chances of prolonged remission.     

Complete remission in two cases of adult T-cell leukemia/lymphoma treated with hyper-CVAD: a case report and review of the literature

BackgroundAcute T-cell leukemia/lymphoma (ATLL) is a post thymic (peripheral) T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Historically, the chemotherapy regimen CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) has been the standard treatment of this rare malignancy. However, its prognosis is poor and median survival in the aggressive variants of ATLL is only 6-10 months. Recently, a more aggressive regimen piloted in Japan, vincristine/cyclophosphamide/doxorubicin/prednisone (VCAP)- doxorubicin/ranimustine/prednisone (AMP)- vindesine/etoposide/carboplatin/prednisone (VECP), has been reported to yield better survival results over biweekly CHOP in a phase III trial. However, the hyper- cyclophosphamide/vincristine/doxorubicin/dexamethasone (CVAD) regimen is a much more frequently used regimen for the treatment of aggressive hematologic malignancies, and has a higher intensity then CHOP. Yet, there is little reported experience with hyper-CVAD regimen in ATLL.Case ReportsWe present 2 patients diagnosed with ATLL who were treated with hyper-CVAD chemotherapy and have achieved a durable complete remission. One of the patients has gone on to receive an allogeneic bone marrow transplantation and has been in complete remission for over 18 months. The other has been in a continuous remission for approximately 12 months. We also review the past published experience with the hyper-CVAD regimen in patients with ATLL.ConclusionA commonly used chemotherapy regimen for aggressive hematologic malignancies, hyper-CVAD, can induce durable remissions in patients with ATLL.     

Phase 2 study of mitozantrone in combination with chlorambucil and prednisolone for relapsed and refractory non-Hodgkins lymphoma

Thirty-six patients with non-Hodgkin's lymphoma (NHL) (comprising patients with refractory or relapsed disease and eight elderly, unfit patients with de novo disease) were treated with mitozantrone, chlorambucil and prednisolone on an out-patient basis. Fifteen patients had low grade (LG) disease, five patients intermediate grade (IG) disease and 16 patients high grade (HG) disease and 31/36 had stage IV disease. All elderly patients had IG or HG disease. The regimen was well-tolerated. After six courses of chemotherapy, there was a 69 per cent response rate with 33 per cent in complete remission. The median duration of remission was 15 months. The overall 3-year projected survival was 38 per cent; 27 per cent for LG disease and 47 per cent for HG and IG disease. Responses did not appear durable for either HG or LG disease unless CR was achieved early on. Three of the eight patients treated de novo (mean age 71 years) have survived disease-free, between 28 and 38 months from entry. This study indicates that mitozantrone-based regimens have promising activity in NHL and require further evaluation. The low toxicity combined with worthwhile remissions make this an attractive first-line option for elderly patients.     

The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors

A prospective study of four cycles of etoposide with ifosfamide and cisplatin (VIP) chemotherapy was conducted in 42 germ cell tumor (GCT) patients who were refractory to cisplatin with etoposide/vinblastine-based therapy. Forty patients were evaluable for response. Ten patients (25%) had a complete response: seven to chemotherapy alone and an additional three patients after surgical resection of viable GCT. With a median follow-up of 15 months, four complete responders relapsed, and six patients (15%) remain in remission. Hematologic and nephrotoxicity were moderately severe. Durable complete responses with VIP as second salvage were achieved and suggests that ifosfamide adds efficacy to standard first-salvage therapy. The observed nephrotoxicity and myelotoxicity are considerations in the design of ifosfamide-cisplatin-based regimens. Hematopoietic growth factors may be useful in ameliorating myelotoxicity. The early use of ifosfamide-based chemotherapy may reduce the nephrotoxicity exacerbated by prior cisplatin. A trial of VIP as first salvage after a relapse from a complete response to platinum-based induction therapy is warranted. The modest proportion of patients who achieve a durable remission to VIP as second salvage emphasizes the need for more efficacious salvage therapy for patients who do not achieve a durable complete response.     

Prolonged remission of refractory lymphomatoid granulomatosis after autologous hemopoietic stem cell transplantation with post-transplantation maintenance interferon

Lymphomatoid granulomatosis (LYG) is a rare Epstein Barr virus (EBV)-associated lymphoproliferative disease. Even with combination chemotherapy, mortality is high. There is no standard therapy for relapsed or refractory disease. There is only one report in the literature of a complete remission with high-dose chemotherapy and autologous stem cell transplantation. This study presents the case of a patient with progressive LYG, who was successfully treated with autologous stem cell transplantation after conditioning with high-dose chemotherapy and total body irradiation. After transplantation, maintenance therapy with interferon alpha 2a was administered for 3.75 years. The patient remains well and in remission 8 years post-transplantation. This is the first report of a durable (>1 year) complete remission after high-dose chemotherapy and autologous stem cell transplantation in LYG. The role of high-dose chemotherapy and autologous stem cell transplantation in relapsed or refractory cases merits further evaluation. The exact place of interferon in treatment of LYG remains to be clarified but is promising.     

Hodgkin's Disease in Children

Fifty-nine children with Hodgkin''s disease were seen over a 34-year period. Compared with Hodgkin''s disease in adults, there was an increased male incidence, especially in the younger children. This was associated with an increased male incidence of lymphocyte-predominant histology. Forty-six patients underwent lymphography as part of their staging, and 13 had staging laparotomies. The 5-year survival for the entire group was 85%, with a median survival of 10 years. Response to radiotherapy in children with Stages I-IIIA disease was: 12 children treated with involved-field radiotherapy after inadequate clinical staging had a 3-year remission rate of 13%, and a median length of remission of 18 months; 24 children treated with extended-field radiotherapy after adequate clinical staging, including lymphography, had a 3-year remission rate of 72%, and a median duration of remission not yet reached; 3 children treated with elective local radiotherapy for Stage IA disease after intensive clinical staging remain in complete remission for periods of up to 34 months. Eight out of 10 children with Stages IIIB-IV disease, treated with combination chemotherapy, achieved complete remission with a 3-year remission rate of 70%; 7 children treated with combination chemotherapy following relapse after radiotherapy all achieved complete remission with a 3-year complete remission rate of 66%. Thirteen children underwent laparotomy and splenectomy as a staging procedure. Five were found to have intra-abdominal disease, including 4 with splenic involvement. These results show that there is no place for involved-field radiotherapy after inadequate clinical staging, in the management of childhood Hodgkin''s disease. Extended-field radiotherapy after adequate staging, and combination chemotherapy, produce results which are as good as those for adults, but the benefits of these treatments and of staging laparotomy must be balanced against the possible complications when they are used in children. These problems are discussed and a scheme of management is proposed.     

Chemotherapeutic Management of Small Bowel Adenocarcinoma Associated with Crohn's Disease

Abstract

Four patients with metastatic primary small bowel adenocarcinoma associated with Crohn's disease were successfully treated with low dose combination chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan with or without gemcitabine. Benefits included prolonged survival, objective responses, response of resistant tumors, downstaging, and a successful secondary complete resection (Ro) with a durable remission.