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.     

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.     

改良ProMACE-CytaBOM方案治疗复发、难治侵袭性NHL的疗效评价

目的评价改良ProMACE-CytaBOM方案治疗复发、难治侵袭性NHL的疗效及安全性。方法回顾性分析2005年5月至2010年9月期间,我院收治的27例复发、难治性侵袭性淋巴瘤患者,其中男19例,女8例,中位年龄47（15～74）岁;均采用改良ProMACE-CytaBOM方案;21天为1周期。结果27例患者均可评价疗效,总有效率51.8%（完全缓解率22.2%）。中位无进展生存期为7月,中位总生存期为19月。B细胞、LDH正常NHL患者中位无进展生存期长于T细胞、LDH高者,差异均有统计学意义（P＜0.05）。B细胞、IPI≤2、LDH正常的NHL患者中位总生存期长于T细胞、IPI＞2、LDH高者,差异均有统计学意义（P＜0.05）。不良反应主要有Ⅱ～Ⅲ度血液学毒性及Ⅰ～Ⅱ度非血液学毒性,6例并发轻度感染,经一般抗生素治疗可控制。结论ProMACE-CytaBOM改良方案治疗复发、难治侵袭性NHL疗效肯定,不良反应可耐受,值得进一步研究。     

Alternating chemotherapy regimen (P-VABEC) for intermediate and high-grade non-Hodgkin's lymphoma of the middle aged and elderly

An intensive third generation regimen (P-VABEC) including adriamycin, etoposide, cyclophosphamide, vincristine, bleomycin and prednisolone was administered to 43 unselected elderly patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 67, 40 per cent were Ann Arbor stage IV, 73 per cent had‘B’ symptoms, 55 per cent had bulky disease, 48 per cent had serum lactate dehydrogenase greater than 450 U/1, 85 per cent had serum thymidine-kinase greater than 4 U/1. Thirty patients were previously untreated. The complete remission (CR) rate was 74 per cent, and the partial remission (PR) rate 23 per cent, with an overall response rate of 97 per cent. The regimen was carried out on an outpatient basis in all patients. No death occurred during therapy. The Kaplan-Meier actuarial survival of all patients at 3-years is 47 per cent, and 50 per cent (16/32) of all patients who attained CR remain alive and in remission at a median of 21+ months (range 6+ to 42+). These results confirm that high remission and failure-free survival rates can be achieved also in elderly unselected patients with aggressive NHL treated with curative intent.     

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.     

A phase II trial of adjuvant low-dose total body irradiation in non-Hodgkin's lymphoma patients following standard CHOP

Because survival results achieved in aggressive NHL with the standard CHOP are not very satisfactory, we investigated adding adjuvant low-dose total body irradiation (LTBI) to standard CHOP in a phase II trial. Thirty-six patients were included between September 1999 and September 2001. All patients were in documented complete remission (CR) after the end of their standard CHOP. LTBI started 4-6 weeks following the last CHOP course and was given in two courses, each with 4 daily fractions of 0.2 Gy, separated by 2 weeks of rest. Patients with bulky disease received involved-field radiotherapy on initial bulky sites starting 4-6 weeks after the last LTBI fraction. Primary end points were disease-free survival (DFS) and overall survival (OS) and the secondary end point was toxicity. The toxicities of LTBI were temporary thrombocytopenia and leucopenia (requiring no transfusions or treatment with growth factors). The 3-year DFS was 61%±9% and the overall survival was 87±6%. Univariate analysis showed time to achieve CR, and whether the patient got LTBI-induced haematological toxicity to be 2 significant prognostic factors affecting DFS. The use of adjuvant LTBI in patients with aggressive NHL in CR after standard chemotherapy is a feasible, non-toxic treatment that is worthy of testing in a future phase III trial.     

The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) is a malignancy that occurs frequently in the elderly with a median age greater than 60 years. However, most chemotherapy trials have included predominantly patients less than 60 years of age. We treated 157 patients with diffuse aggressive NHL between September 1982 and May 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), procarbazine, bleomycin, vincristine, and prednisone (CAP/BOP). There were no treatment exclusions for age. Patients in this study ranged in age from 15 to 91 years (median, 63) with 112 patients greater than or equal to 60 years of age. The overall complete remission (CR) rate was 65% with no significant difference for age less than 60 (76%) v age greater than or equal to 60 (61%) (P = .18). With a median 36-month follow-up (range, 22 to 65 months), the overall 5-year survival was 42%. The patients less than 60 years old had a 62% 5-year survival in contrast to a 34% 5-year survival in those patients greater than or equal to age 60 (P = .01). The deaths attributed to tumor or treatment-related toxicity were similar above and below age 60. The difference in survival was due to other causes of death not obviously related to the lymphoma or its therapy-occurring in 22% of patients greater than or equal to 60 years of age but only 2% of patients less than 60 years (P = .005). Our data supports the position that aggressive NHL in elderly patients is not significantly less responsive than in younger patients; however, the inclusion of older patients in clinical trials will decrease the overall survival secondary to deaths due to apparently unrelated causes.     

The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma

BACKGROUND: The International Prognostic Index (IPI) effectively separates aggressive lymphomas into four groups with significantly different responses to therapy and survival. The authors have applied the IPI to evaluate a series of patients with human immunodeficiency virus (HIV) related lymphoma, a disease for which treatment strategies are still controversial and prognostic indicators are therefore particularly important. METHODS: Sixty-nine consecutive evaluable patients with HIV-related systemic non-Hodgkin lymphoma (NHL) diagnosed at a single Institution during a 10-year period were analyzed. Primary cerebral lymphoma was not considered. Forty-nine patients (71%) received aggressive combination chemotherapy (CT), 45 of whom were treated with the same program: cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, and methotrexate with lecuovorin and prednisone (ProMACE-CytaBOM). Univariate and multivariate methods were used for statistical analysis. End points were response to treatment in patients receiving aggressive CT and survival of treated patients and all patients. RESULTS: According to age-adjusted IPI, 5 patients (7%) belonged to the low risk group, 12 (17%) to the low-intermediate risk group, 16 (23%) to the high-intermediate risk group, and 36 (52%) to the high risk group. Among the four groups with increasing IPI scores, the mean CD4 cell count at NHL diagnosis was 313, 230, 151, and 72/microL, respectively (P = 0.0085). The complete response (CR) rates were 100%, 88%, 50%, and 32% (P = 0. 0001) and the median survival of all patients was >60, 17, 10.9, and 6.8 months (P = 0.0002) for patients with low, low-intermediate, high-intermediate, and high risk IPI scores, respectively. In multivariate analysis, among patients receiving aggressive CT, high risk IPI (P = 0.013) and systemic symptoms (P = 0.014) were the only parameters related to CR, and high risk IPI (P = 0.016) and achievement of CR (P < 0.001) were the only parameters related to survival. When all patients were considered, high risk IPI had significant prognostic value for overall survival (P = 0.01), as did age (P = 0.019) and achievement of CR (P < 0.001). CONCLUSIONS: IPI was a reliable prognostic indicator in an unselected series of patients with HIV-related systemic NHL. The outcomes of patients without high risk IPI treated with aggressive CT were similar to those expected for HIV negative patients with lymphoma. However more than half of patients with HIV-related NHL had IPI high risk disease, and their outcomes were poor even after aggressive CT. The degree of immunodeficiency was related to increasing IPI score, suggesting that immunodeficiency may be an important factor contributing to the aggressive clinical presentation of lymphoma.     

Prophylactic intrathecal methotrexate and hydrocortisone reduces central nervous system recurrence and improves survival in aggressive non-hodgkin lymphoma

BACKGROUND: Central nervous system (CNS) recurrence is almost invariably fatal in patients with aggressive non-Hodgkin lymphoma (NHL). Although some protocols are intended to prevent CNS disease, the value of CNS prophylaxis in patients with aggressive NHL remains to be determined. METHODS: We retrospectively analyzed a cohort of 68 adults with NHL who had been treated uniformly with systemic chemotherapy and had attained complete remission (CR) of disease. Patients ranged in age from 15 to 77 years (median, 56 years). Median follow-up after CR was 40 months. After CR was attained, 29 patients (Group A) received CNS prophylaxis consisting of four doses of intrathecal methotrexate 10 mg/m(2) and hydrocortisone 15 mg/m(2) as soon as they could tolerate it. The other 39 patients (Group B) did not receive CNS prophylaxis. RESULTS: Although bulky mass (45% vs. 21%, P = 0.03) was more frequent in Group A than in Group B, none of the patients in Group A experienced CNS recurrence (0%), whereas CNS recurrence occurred in six patients in Group B (15%). This difference was significant (P = 0.03). Multivariate logistic regression analysis for CNS recurrence identified no CNS prophylaxis (P = 0.01) and bone marrow involvement (P = 0.02) as independent predictors. Among patients without CNS disease, systemic recurrence occurred in 5 patients in Group A and in 11 patients in Group B (P = 0.12). The 5-year overall survival rate from CR was 80% in Group A and 58% in Group B (P = 0.05). The 5-year recurrence-free survival rate from CR was 85% in Group A and 51% in Group B (P = 0.01). CONCLUSIONS: Prophylactic intrathecal methotrexate and hydrocortisone injection reduces the incidence of CNS recurrence following CR in patients with aggressive NHL and improves the chance of long-term survival.     

Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi

Patients with aggressive NHL who fail initial treatment or subsequently relapse have a very poor outcome and less than 20-25% achieve a prolonged disease-free interval with salvage therapies. To improve the outcome of patients with refractory aggressive NHL not suitable for High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT), the efficacy of a combination of gemcitabine, vinorelbine, procarbazine and prednisone (ViGePP) were tested. Between November 1999 and September 2002, 69 patients with relapsed or refractory aggressive NHL were treated with ViGePP regimen, every 4 weeks up to six courses. At the end of planned chemotherapy patients could receive additional radiotherapy on residual masses or on sites of previously bulky disease. Sixty-six patients were available for evaluation of study end-points. Thirty patients were refractory to therapy and 36 patients had relapsed after remission obtained with previous therapy. At the end of therapy, complete remission (CR) rate was 23%, 3-year relapse free survival rate was 40% and 3-year overall survival rate was 25% for the whole series (29% and 20% for relapsed and refractory patients, respectively). Patients achieving CR with ViGePP had a significantly better survival as compared with the remaining ones (p = 0.0003). ViGePP as used in the present setting has demonstrated a promising activity, comparable to other conventional dose regimens. Although CR was achieved only in a minority of patients, this was durable in a significant proportion of them. This regimen should be tested in less heavily pre-treated patients and probably in combination with new active agents such Rituximab. Further developments of this combination are warranted.     

A risk factor for relapse in Hodgkin's disease: Female gender?

A retrospective study of 163 patients with Hodgkin's disease treated between 1969 and 1987 was performed to identify adverse prognostic factors. One hundred and thirty-five patients (83 per cent) attained a complete remission and 42 (31 per cent) of these have relapsed (median follow-up--43 months). Using multivariate analysis, no independent factors predicted for the event of relapse. However, analysis of disease-free survival revealed that females fared significantly worse than males (p less than 0.05) and this was independent of other prognostic variables. Female sex has not been recognized as an independent prognostic factor predictive of inferior survival and inferior disease-free survival.     

A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma.

This Phase II trial was undertaken to determine the safety, toxicity, and potential efficacy of the B-cell restricted immunotoxin anti-B4-blocked ricin (Anti-B4-bR) when administered as adjuvant therapy to patients in complete remission (CR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (NHL). Forty-nine patients with B-cell NHL in CR 46-202 days (median, 112 days) post-ABMT received Anti-B4-bR at a dose of 30 microg/kg lean body weight/day for 7 days by continuous i.v. infusion. Patients were eligible for up to two additional courses of therapy at 14-day intervals. A total of 83 courses of Anti-B4-bR were administered, with 31 patients receiving two or more courses of therapy. The mean serum level on day 7 of the first course was 0.77+/-0.41 nM. Reversible toxicities included hepatic transaminase elevations, thrombocytopenia, myalgias, fatigue, nausea, hypoalbuminemia, and dyspnea. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) responses occurred in 23 patients at a median of 22 days from the initiation of Anti-B4-bR therapy (range, 11-100 days). The 4-year disease-free survival and overall survival are estimated at 56 and 72%, respectively. Twenty-six patients remain in CR after a median follow-up of 54.5 months. This study demonstrates that Anti-B4-bR can be administered safely to patients as adjuvant therapy early after ABMT for B-cell NHL. The toxicities are tolerable and reversible. Although the early estimate of disease-free survival was very encouraging in this single-armed trial, the 4-year follow-up data demonstrate continued relapse.     

Autologous hematopoietic stem cell transplantation for aggressive B-cell non-Hodgkin's lymphoma

To evaluate the results of high-dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with diffuse B-cell aggressive non-Hodgkin's lymphoma(NHL). Between 1991 and 2004, 25 patients who did not achieve complete remission and 26 in complete remission from conventional chemotherapy received HDC-ASCT. Of 25 patients with refractory NHL,14 were chemotherapy-sensitive before HDT-ASCT and 11 were chemotherapy-resistant. CR was achieved after HDC-ASCT in 50% of 14 chemotherapy sensitive patients and in none of 11 chemotherapy-resistant patients. The 5-year probability of event-free survival for chemotherapy-sensitive and chemotherapy-resistant patients was 51.3% and 20.8%, respectively (p<0.05, log-rank test). Moreover, the 5-year probability of event-free survival for patients in the low-risk group with International Prognostic Index (IPI) and in the high-risk group with IPI was 75.0% and 16.3%, respectively (p<0.05, log-rank test). HDT-ASCT should be considered for patients with refractory aggressive NHL who are chemotherapy-sensitive rather than chemotherapy-resistant. Twenty-six patients in complete remission received consolidation therapy with HDT-ASCT. The 5-year probability of disease-free survival for patients in the low-risk group and in the high-risk group was 68.8% and 60.0%,respectively (p = 0.9 6). HDT-ASCT should be considered for patients at high risk who achieve complete remission after induction treatment. In future, HDT-ASCT combined with rituximab as induction therapy or as consolidation therapy is needed for patients with aggressive NHL in the high-risk group.     

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.     

CEOP treatment results and validity of the International Prognostic Index in Chinese patients with aggressive non-Hodgkin's lymphoma

From 1991 to 1997, we have treated 78 newly diagnosed patients with aggressive non-Hodgkin's lymphoma with a modified CHOP regimen in which epirubicin (60 mg/m2) was used in place of doxorubicin (50 mg/m2), i.e. CEOP (cyclophosphamide, epirubicin, vincristine and prednisolone). The median age was 41 years (range: 17 to 67). Sixty-four (82 per cent) had diffuse large cell (Working Formulation category G) histology. The median LDH level was 453 u/l. Thirty-three (42.3 per cent) and 45 (57.7 per cent) had stage I/II and stage III/IV disease, respectively. Fifty-five of 78 (71 per cent) CEOP-treated patients achieved CR, and the projected DFS and OS were both 65 per cent. In an earlier cohort of patients (from 1985-1991) treated with second or third-generation chemotherapy regimens (m-BACOD, MACOP-B, ProMACE-CytaBOM), CR was achieved in 95/123 (77 per cent) patients and the projected DFS and OS were 62 per cent and 55 per cent. There was no significant difference in the clinical characteristics, CR rates (p = 0.26), DFS (p = 0.38) or OS (p = 0.68) between patients who received CEOP or second/third-generation chemotherapy regimens. Of the patients treated with CEOP, 37.9 per cent, 28.8 per cent, 24.2 per cent and 9.1 per cent were in the age-adjusted International Index L, LI, HI and H risk groups, with CR rates of 82 per cent and 57 per cent in the L/LI and HI/H risk groups (p = 0.03). Moreover, patients in the L, LI and HI/H risk groups had significantly different projected DFS (87 per cent, 62 per cent and 39 per cent, p = 0.02) and OS (85 per cent, 80 per cent and 36 per cent, p = 0.006). In conclusion, CEOP is an effective regimen and the age-adjusted International Index is valid for Chinese patients with aggressive NHL.     

Impact of three courses of intensified CHOP prior to high-dose sequential therapy followed by autologous stem-cell transplantation as first-line treatment in poor-risk, aggressive non-hodgkin's lymphoma: comparative analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40.

PURPOSE: Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. PATIENTS AND METHODS: Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age < or = 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5x upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). RESULTS: Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1x ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. CONCLUSION: In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.     

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.     

Treatment of large cell lymphoma in elderly patients with a mitoxantrone,cyclophosphamide, etoposide,and prednisone regimen: long-term follow-up results

BACKGROUND: Patients with aggressive non-Hodgkin lymphoma (NHL) require intensive and extensive therapy, which seems impracticable in elderly patients due to hematologic and extrahematologic toxicity. Consequent dose reduction and therapy attenuation can reduce treatment-related toxicity but also decreases therapeutic efficacy. Thus, age represents a fundamental prognostic factor that has a profound influence on both therapeutic decisions and patient outcome. METHODS: Between January, 1990 and June, 1997, 145 patients age > 64 years (median age, 72.3 years) with a diagnosis of aggressive NHL were treated on a chemotherapy regimen that consisted of mitoxantrone, cyclophosphamide, etoposide, and prednisone. RESULTS: Ninety-one patients (63%) achieved complete remission, and 48 patients (33%) achieved partial remission, for an overall response rate of 96%. Six patients (4%) were resistant to therapy. The overall survival rate, with a median follow-up of 66 months, was 44%, and the failure free survival rate was 42%. The disease free survival rate was 63.5%, with a median follow-up of 60 months. Multivariate survival analysis showed that the achievement of complete remission was the single most important prognostic factor, which was associated significantly with longer survival (P < 0.0001). Toxicity was moderate, with 5 deaths (3%) due to complications related to therapy. CONCLUSIONS: The current results confirm that a protocol devised specifically for elderly patients may reduce toxicity and allow longer overall survival in this particular subset of patients.     

Factors affecting remission and survival in patients with advanced Hodgkin's disease treated with MVPP

One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.     

Prognostic significance of the immunophenotype versus the International Prognostic Index in aggressive non-Hodgkin's lymphoma

The International Prognostic Index (IPI) is currently the most widely accepted prognostic factor system for patients with aggressive non-Hodgkin's lymphoma (NHL). However, in constructing the model, the immunophenotype of the disease was not used as an independent variable. The purpose of the present study was to assess and compare the prognostic significance of the immunophenotype (B-cell vs. T-cell) of aggressive NHL with other well-established prognostic determinants, in particular the IPI. Between January 1995 and December 2000, a retrospective analysis was conducted of clinical and pathological data on 181 patients aged = 15 years who had been newly diagnosed with aggressive NHL. All pathology slides were reviewed and defined according to the Revised European-American Lymphoma classification. Forty-one patients (23%) had T-cell lymphoma and 140 patients (77%) had B-cell lymphoma. Diffuse large B-cell lymphoma and unspecified peripheral T-cell lymphoma were the 2 most common entities, comprising 63% and 14% of patients, respectively. Most of the pretreatment characteristics, including IPI risk groups, were not significantly different between B-cell and T-cell lymphomas. The rates of complete remission (71% vs. 54%, P = 0.038) and progressive disease (39% vs. 63%, P = 0.023) significantly favored patients with B-cell lymphoma. With a median follow-up time of 31 months (range, 10-81 months), the 5-year overall survival (49% vs. 27%; P < 0.001) and event-free survival (35% vs. 10%; P < 0.001) were significantly better in B-cell lymphoma. The 5-year disease-free survival was also in favor of the B-cell group (48% vs. 21%; P = 0.086). Patients with T-cell lymphoma yielded inferior survival in all IPI risk groups. Multivariate analysis revealed T-cell lymphoma as the most significant factor associated with short overall survival (relative risk [RR], 3.4; 95% CI, 1.9-5.9) and event-free survival (RR 2.7, 95% CI, 1.7-4.3). When a second multivariate analysis was done using IPI (age, stage, performance status, number of extranodal sites, and serum lactate dehydrogenase) as one independent variable, T-cell phenotype remained the strongest factor affecting the survival of patients (P < 0.001). T-cell lymphoma is an independent prognostic factor, the significance of which is at least comparable to the IPI for patients with aggressive NHL.