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.     

A phase II trial of ProMACE-CytaBOM in previously untreated non-Hodgkin's lymphoma of intermediate- or high-grade histology.

Between November 1985 and June 1989 the aggressive combination chemotherapy programme ProMACE-CytaBOM was used at a community-based hospital as primary treatment for non-Hodgkin's lymphoma (NHL) of intermediate or high-grade histology in Ann-Arbor stages IB-IV. The 53 patients entering the study represented 90 per cent of all consecutive eligible patients with NHL diagnosed during the time period considered. Their median age was 54 years and median observation time was 36 months. Of 50 patients evaluable for response, 35 (70 per cent) achieved complete remission (CR), seven (14 per cent) partial remission, and five (10 per cent) were refractory. Treatment was given on an outpatient basis. Actually delivered drug doses ranged from 88 per cent to 97 per cent of the theoretical doses. Life-threatening toxicity was experienced by four patients. Treatment was stopped in three cases (6 per cent) because of toxicity and there was one treatment-related death. Actuarial 2-year disease-free survival of patients in CR was 73 per cent. Overall actuarial 3-year survival and disease-free survival were 67 per cent and 51 per cent respectively. High LDH level was a significant adverse prognostic factor both for achievement of CR (P less than 0.005) and for survival (P less than 0.0002). Age was of no prognostic importance. We conclude that ProMACE-CytaBOM is an effective, easy to administer and well-tolerated regimen for patients with aggressive NHL.     

Non-Hodgkin's lymphoma of unfavourable histology: a multivariate analysis of factors predicting the response to CHOP

Forty-eight patients with de novo non-Hodgkin's lymphoma (NHL) of unfavourable biology received CHOP as first-line chemotherapy. A complete remission (CR) was achieved in 64.5 per cent patients. Overall 4-year projected survival was 48 per cent with a median follow-up of 40.5 months. Two pretreatment characteristics, high LDH serum levels and bulky abdominal disease, were negatively associated with survival at the proportional hazards regression model and were used to calculate each patient's relative-risk. Such analysis allowed to identify two prognostic subgroups according to their outcome to CHOP. Firstly, a high-risk subgroup that showed an 8 per cent CR rate, most patients dying within the first year after diagnosis. Secondly, a low-risk subgroup that showed an 83.5 per cent CR rate and a 4-year project survival of 66 per cent. From the above results two major conclusions can be drawn: (1) the CHOP combination is an effective treatment for unfavourable NHL patients with a low relative-risk and (2) new therapeutic approaches should be explored for NHL patients with a high relative-risk at diagnosis.     

BACOD方案治疗复发及难治性非霍奇金淋巴瘤的临床研究

 目的　观察BACOD方案治疗复发及难治性非霍奇金淋巴瘤（NHL）的疗效及患者不良反应。方法　65例复发及难治性NHL患者,采用BACOD方案进行化疗,具体为：博莱霉素10 mg／m2,静脉滴注,第2、9天;环磷酰胺750 mg／m2,静脉滴注,第1天;长春地辛3 mg／m2,静脉注射,第1、8天;阿糖胞苷150 mg／m2,静脉滴注,第2天至第5天;地塞米松10 mg／m2,静脉滴注,第1天至第7天,3周为1个疗程。结果　完全缓解18例,部分缓解30例,稳定13例,进展4例,有效率70.8 %。有效患者中位缓解时间 10个月（2～35个月）。1年生存率32.3 %,2年生存率24.6 %。患者主要不良反应为骨髓抑制。结论　BACOD方案可作为复发及难治性NHL的解救方案。     

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome.

Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of < 10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 x 10(9)/l prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p = 0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p 0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.     

Prognostic factors in high and intermediate grade non-Hodgkin's lymphoma

An analysis of prognostic factors has been performed on 260 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) treated over an 11-year period between 1975 and 1986. The overall 5-year survival rate was 50% with a median follow-up of 72 months. Over 20 clinical, radiological and laboratory parameters have been studied, including variables reported to be important indicators of prognosis in previous series, and these variables have been subjected to univariate and multivariate analysis. Attainment of complete remission (CR) was the most important predictor of overall survival, low serum lactate dehydrogenase (LDH), limited stage disease and a high serum albumin were also independently associated with prolonged survival in multivariate analysis. After removing remission status from the model, Ann Arbor clinical stage became the most significant pre-treatment prognostic indicator. Sixty-five per cent of patients achieved CR, and a discriminant analysis showed that failure to attain CR was associated with advanced stage disease, constitutional symptoms, increasing patient age, a low serum albumin and the presence of bulk disease. Advanced clinical stage and an elevated serum LDH predicted independently for a poor relapse-free survival, and reduced overall survival following CR. There was no significant correlation between histological subtype in the Kiel classification and prognosis. This study confirms the prognostic significance of remission status and Ann Arbor clinical stage, and illustrates additional factors including serum levels of albumin and LDH, which serve to enhance the pre-treatment prognostic evaluation of patients with unfavourable histology NHL.     

Prolonged disease-free survival in pediatric non-Hodgkin's lymphoma using ifosfamide-containing combination chemotherapy.

Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival.     

Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Failure of IMVP-16 as second-line treatment for relapsed or refractory high grade non-Hodgkin's lymphoma.

The British National Lymphoma Investigation (BNLI) has assessed the use of an IMVP-16 regimen (ifosfamide, methotrexate, VP-16) in 46 patients with high grade non-Hodgkin's lymphoma (NHL) who on first-line chemotherapy either failed to attain a complete remission or relapsed. Seventeen patients responded to IMVP-16 but only five (11 per cent) went into a complete remission (CR), 12 (26 per cent) had a partial remission (PR) and 29 (63 per cent) showed no response (NR). CR after IMVP-16 has been maintained in only one case (36 months). The results of this study imply that the use of this IMVP-16 protocol as second-line treatment for patients with recurrent high grade NHL is unsuccessful and alternative salvage regimens should be sought.     

Feasibility of High-Dose Chemotherapy without Stem Cell Support as a First-Line Treatment for Non-Hodgkin's Aggressive Lymphoma: A Pilot Study

A regimen which incorporates cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) is the standard treatment for patients with non-Hodgkin's lymphoma (NHL), but it has not been effective in patients with aggressive NHL who are at high risk. The aim of the present trial was to investigate the feasibility of high-dose chemotherapy (HDC) without stem cell support as a first-line treatment. The primary endpoint was a complete remission rate. The second endpoint was survival. Fourteen patients with aggressive NHL entered the study and were treated according to the K93 protocol (3 cycles of CHOP, high-dose etoposide and ifosfamide, and high-dose methotrexate) Eleven patients (79%) achieved complete remission (CR) and two (14%) achieved partial remission (PR). Overall survival (OS) after five years was 79%. The actuarial five year disease free survival (DFS) for the eleven cases of CR was 75%. During chemotherapy, grade IV hematologic toxicity was observed in all patients and grade IV non-hematologic toxicity in only one patient, who experienced oral ulcers. Peripheral blood stem cell (PBSC) apheresis was performed in eight cases. One harvesting was enough to provide an adequate number of CD34+ cells for the subsequent PBSC transplantation (PBSCT).

In conclusion our study confirmed the efficacy of the K93 protocol in obtaining a good response (CR + PR) rate and a very good DFS rate in most cases of aggressive NHL, with acceptable toxicity. This regimen may improve the outcome in cases of aggressive NHL without stem cell support. It seems worthwhile to conduct a randomized controlled study comparing the K93 protocol with the standard CHOP regimen.     

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease and non-Hodgkin's lymphoma. The Swedish Lymphoma Study Group

One hundred and three patients with recurrent or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) were retrospectively studied. Thirty-seven of the 44 patients with HD, 34/47 with high-grade malignant and 9/12 with low-grade malignant NHL were evaluable for response. Of the 37 evaluable patients with HD, 16 (43%) achieved complete remission (CR) and 4 partial remission (PR), giving a total response rate of 54%. Of the 34 evaluable patients with high-grade NHL, 5 achieved CR and 8 PR, giving a response rate of 38%. Of 9 evaluable patients with low-grade NHL, 2 achieved CR. The main toxicity was leukopenia, thrombocytopenia and infections. Twenty-six per cent of the patients developed septicaemia, which was fatal in 6 cases (6%). We conclude that MIME as salvage regimen can induce complete remissions in lymphoma patients, particularly in HD with previous heavy treatment, and that it is relatively well tolerated.     

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.     

Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia

BACKGROUND: Adult Burkitt-type lymphoma (BL) and acute lymphoblastic leukemia (B-ALL) are rare entities composing 1% to 5% of non-Hodgkin lymphomas NHL) or ALL. Prognosis of BL and B-ALL has been poor with conventional NHL or ALL regimens, but has improved with dose-intensive regimens. METHODS: To evaluate the addition of rituximab, a CD20 monoclonal antibody, to intensive chemotherapy in adults with BL or B-ALL, 31 patients with newly diagnosed BL or B-ALL received the hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen with rituximab. Their median age was 46 years; 29% were 60 years or older. Rituximab 375 mg/m(2) was given on Days 1 and 11 of hyper-CVAD courses and on Days 1 and 8 of methotrexate and cytarabine courses. RESULTS: Complete remission (complete response [CR]) was achieved in 24 of 28 (86%) evaluable patients; 3 had a partial response, and 1 had resistant disease. There were no induction deaths. The 3-year overall survival (OS), event-free survival, and disease-free survival rates were 89%, 80%, and 88%, respectively. Nine elderly patients achieved CR with all of them in continuous CR (except 1 death in CR from infection), with a 3-year OS rate of 89%. Multivariate analysis of current and historical (those treated with hyper-CVAD alone) groups identified age and treatment with rituximab as favorable factors. CONCLUSIONS: The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients.     

DHAP方案治疗复发和难治性中、高度恶性非霍奇金淋巴瘤的初步观察

背景和目的:复发和耐药非霍奇金淋巴瘤的治疗十分棘手,国外文献报道DHAP方案取得较好疗效,但国内尚未见报道。我们采用DHAP方案治疗复发和难治性非霍奇金淋巴瘤,进一步评价该方案的疗效及毒性。方法:17例复发和10例难治性非霍奇金淋巴瘤患者接受DHAP方案(顺铂20mg/m2,第1～5天;阿糖胞苷1g/m2,q12h,第1～2天;地塞米松40mg,第1～4天)化疗,3～4周重复一次。4例患者进一步进行了自体外周血干细胞移植支持下的超大剂量化疗。结果:CR8例(29.6%),PR4例(14.8%),有效率为44.4%(12/27)。有效患者中位缓解时间4.8个月。DHAP方案治疗后中位生存时间8.3个月,1年生存率为30.8%,2年生存率为19.3%。主要不良反应为骨髓抑制,主要表现为白细胞下降和血小板下降,Ⅲ～Ⅳ度白细胞下降占59.3%(16/27),其中3例(11.1%)患者因粒细胞缺乏出现感染性发热;Ⅲ～Ⅳ度血小板下降占81.5%(22/27),5例(18.5%)患者进行了预防性血小板输注。结论:DHAP是治疗复发和难治性中高度恶性非霍奇金淋巴瘤的有效方案,但仍存在有效率较低,缓解期较短的缺点,且骨髓毒性严重,尤其是血小板和白细胞下降。对于敏感复发的患者,DHAP方案取得完全缓解后,应争取行外周血干细胞移植支持下的大剂量化疗,以延长缓解期和提高长期生存率。     

左旋门冬酰胺酶联合DICE方案治疗复发难治性非霍奇金淋巴瘤的疗效和安全性

 【摘要】　目的　探讨左旋门冬酰胺酶（L-Asp）联合DICE方案治疗复发难治性非霍奇金淋巴瘤（NHL）的疗效和安全性。方法　31例复发难治性NHL患者接受L-Asp联合DICE方案治疗,每位患者计划接受2～6个周期化疗。结果　在所有可评估的31例患者中,11例（35.5 %）完全缓解（CR）,14例（45.2 %）部分缓解（PR）,2例稳定,总有效（CR+PR）率为80.7 %。有效患者中位生存期为8个月（2～30个月）。全组患者预计1年生存率为43.3 %,2年生存率为32.5 %。主要不良反应为骨髓抑制、消化道反应、变态反应和水肿。治疗期间未观察到治疗相关性死亡。结论　L-Asp联合DICE方案治疗复发难治性NHL是有效和安全的。     

Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.     

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.     

DICE方案治疗复发或耐药中高度恶性非霍奇金淋巴瘤

背景与目的:复发或耐药非霍奇金淋巴瘤(non鄄Hodgkin蒺slymphoma,NHL)目前尚无标准的解救化疗方案,DICE、ESHAP、MINE和EPOCH等常见的解救治疗方案缓解率仅为30%～70%。本文旨在观察DICE方案作为解救化疗方案治疗复发或耐药中高度恶性NHL的疗效和安全性。方法:选取35例复发或耐药的中高度恶性NHL患者,其中T细胞和B细胞NHL分别为14和21例,既往接受过以CHOP或CHOP样方案为主中位6周期(2～12个周期)的化疗,采用DICE方案进行解救治疗。结果:35例患者接受了中位4周期(2～7个周期)的DICE方案化疗,所有患者均可评价疗效和不良反应。总的客观有效率为74.3%,完全缓解率为31.4%;中位缓解时间为4个月(1～30个月),中位至治疗失败时间为7个月(2～34个月),中位生存期为14个月(3～51个月),实际2年生存率为33.3%。T细胞和B细胞NHL的有效率分别为85.7%(12/14)和66.7%(14/21),完全缓解率分别为50.0%(7/14)和19.0%(4/21)(P=0.073)。LDH升高和伴有巨大肿块是影响解救治疗疗效的高危因素(P<0.05),DICE解救疗效是复发耐药患者生存期的独立预后因素(P=0.001)。主要不良反应为骨髓抑制,Ⅲ～Ⅳ度粒细胞和血小板减少的发生率分别为71.4%和8.6%。结论:DICE方案是复发或耐药中高度恶性NHL安全有效的解救治疗方案。LDH升高和伴有巨大     

Feasibility of high-dose chemotherapy without stem cell support as a first-line treatment for non-Hodgkin's aggressive lymphoma: a pilot study

A regimen which incorporates cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) is the standard treatment for patients with non-Hodgkin's lymphoma (NHL), but it has not been effective in patients with aggressive NHL who are at high risk. The aim of the present trial was to investigate the feasibility of high-dose chemotherapy (HDC) without stem cell support as a first-line treatment. The primary endpoint was a complete remission rate. The second endpoint was survival. Fourteen patients with aggressive NHL entered the study and were treated according to the K93 protocol (3 cycles of CHOP, high-dose etoposide and ifosfamide, and high-dose methotrexate) Eleven patients (79%) achieved complete remission (CR) and two (14%) achieved partial remission (PR). Overall survival (OS) after five years was 79%. The actuarial five year disease free survival (DFS) for the eleven cases of CR was 75%. During chemotherapy, grade IV hematologic toxicity was observed in all patients and grade IV non-hematologic toxicity in only one patient, who experienced oral ulcers. Peripheral blood stem cell (PBSC) apheresis was performed in eight cases. One harvesting was enough to provide an adequate number of CD34+ cells for the subsequent PBSC transplantation (PBSCT). In conclusion our study confirmed the efficacy of the K93 protocol in obtaining a good response (CR + PR) rate and a very good DFS rate in most cases of aggressive NHL, with acceptable toxicity. This regimen may improve the outcome in cases of aggressive NHL without stem cell support. It seems worthwhile to conduct a randomized controlled study comparing the K93 protocol with the standard CHOP regimen.     

An alternating chemotherapy combination (MACOBLE) for intermediate and high-grade non-Hodgkin's lymphoma.

From June 1983 to February 1986, 48 patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL) received a CHOP based combination with the addition of etoposide on days 1 and 2, bleomycin days 1 and 10 and methotrexate 1.5 g/m2 on day 10 (MACOBLE). Their median age was 59 years, 20 (42 per cent) had an ECOG performance status (PS) of 2 or 3, 24 (50 per cent) had stage IV disease, 25 (52 per cent) B symptoms and 21 (44 per cent) bulk (greater than 10 cm) disease. With a median follow-up of 62 months, 12 patients are alive, 10 of whom are disease-free. Median overall survival was 13 months (95 per cent confidence interval 6-23 months) with actuarial 5-year survival of 25 per cent (95 per cent confidence interval 13-37 per cent). Factors associated with inferior survival were ECOG PS 2 or 3 (P = 0.004), B symptoms (P = 0.013) and bulk disease (P = 0.017). These data suggest that, when treating an unselected patient population, attempts to increase the intensity of first-line chemotherapy may not improve the outcome.