Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome

The appropriate therapy for limited-stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL), chemotherapy is often omitted; however, it is unknown whether this impacts the risk of relapse. Herein, we compared the outcome of patients with limited-stage NLPHL treated in an era in which ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy was routinely incorporated into the primary therapy to an earlier era in which radiotherapy (RT) was used as a single modality. Using the British Columbia Cancer Agency Lymphoid Cancer Database, 88 patients with limited-stage NLPHL (stage 1A/1B or 2A, nonbulky disease < 10 cm) were identified. Treatment followed era-specific guidelines: before 1993, (n = 32) RT alone; and 1993 to present (n = 56), ABVD-like chemotherapy for 2 cycles followed by RT with the exception of 14 patients who received ABVD chemotherapy alone. Most patients were male (75%) with stage I disease (61%). In an era-to-era comparison, the 10-year time to progression (98% vs 76% P = .0074), progression-free survival (91% vs 65% P = .0024), and OS (93% vs 84%, P = .074) favored the ABVD treatment era compared with the RT alone era. Treating limited-stage NLPHL similarly to CHL may improve outcome compared with the use of radiation alone.     

Cyclic delivery of MOPP and ABVD combinations in Stage IV Hodgkin's disease: rationale, background studies, and recent results

This paper summarizes the experience achieved at the Cancer Institute of Milan with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in various stages of Hodgkin's disease, with special emphasis on the cyclic delivery of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) and ABVD in the primary treatment of stage IV disease. Six cycles of ABVD yielded a complete remission (CR) rate (71%) similar to that of MOPP (63%). ABVD combined with radiotherapy in 153 patients with stage IIB, IIIA, or IIIB disease was superior to MOPP plus radiotherapy in the CR induction (94% vs 79%, P less than 0.01), particularly in the presence of nodular sclerosis histology (P less than 0.03) and B symptoms (P = 0.01), as well as in the relapse-free survival of patients with pathologic stage IIIA disease (ABVD, 100%; MOPP, 68%; P = 0.02). Total survival was similar between the two treatment groups, but, compared to MOPP, ABVD chemotherapy was associated with a lower incidence of delayed toxic effects such as azoospermia, prolonged amenorrhea, and cancerigenesis. ABVD induced CR in 59% of 54 patients resistant to MOPP; 37.5% of the complete responders remain alive and disease-free at 5 years. The cyclic delivery of MOPP and ABVD was significantly superior to that of MOPP alone in terms of CR (92% vs 71%; P = 0.02), freedom from disease progression (70% vs 37%; P less than 0.0001), and relapse-free survival (77% vs 47%; P less than 0.01) at 5 years. Toxic effects were similar between the two treatment groups, but there was a higher incidence of vomiting and alopecia following ABVD chemotherapy; in the group given MOPP alone, one patient who had previously failed extensive irradiation developed acute nonlymphocytic leukemia. ABVD is confirmed to be an effective regimen that is non-cross-resistant to MOPP and devoid of late morbidity. Therefore, its administration, when alternated monthly with MOPP, offers the possibility to improve the cure rate of Hodgkin's disease.     

Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA)

From 1989 to 1996, 533 eligible patients with stage IIIB/IV Hodgkin lymphoma (HL) were randomly assigned to receive 6 cycles of hybrid MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine; n = 266) or ABVPP (doxorubicin, bleomycin, vinblastine, procarbazine, prednisone; n = 267). Patients in complete remission (CR) or partial response of at least 75% after 6 cycles received 2 cycles of consolidation chemotherapy (CT) (n = 208) or subtotal nodal irradiation (RT) (n = 210). A better survival probability was observed after ABVPP alone: the 10-year overall survival (OS) estimates were 90% for ABVPP x 8, 78% for MOPP/ABV x 8, 82% for MOPP/ABV with RT, and 77% for ABVPP x 6 with RT (P = .03); and the 10-year disease-free survival (DFS) estimates were 70%, 76%, 79%, and 76%, respectively (P = .09). The 10-year DFS estimates for patients treated with consolidation CT or RT were 73% and 78% (P = .07), and OS estimates were 84% and 79%, respectively (P = .29). These results showed that RT was not superior to consolidation CT after a doxorubicin-induced CR in patients with advanced HL. An analysis of competing risks identified age more than 45 years as a significant risk factor for death, relapse, and second cancers. Prospective evaluation of late adverse events may improve the management of patients with HL.     

Early‐stage Hodgkin lymphoma outcomes after combined modality therapy according to the post‐chemotherapy 5‐point score: can residual pet‐positive disease be cured with radiotherapy alone?

Early‐stage classical Hodgkin lymphoma (HL) patients are evaluated by an end‐of‐chemotherapy positron emission tomography‐computed tomography (eoc‐PET‐CT) after doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and before radiation therapy (RT). We determined freedom from progression (FFP) in patients treated with ABVD and RT according to the eoc‐PET‐CT 5‐point score (5PS). Secondarily, we assessed whether patients with a positive eoc‐PET‐CT (5PS of 4–5) can be cured with RT alone. The cohort comprised 174 patients treated for stage I‐II HL with ABVD and RT alone. ABVD was given with a median of four cycles and RT with a median dose of 30·6 Gy. Five‐year FFP was 97%. Five‐year FFP was 100% (0 relapses/98 patients) for patients with a 5PS of 1–2, 97% (2/65) for a 5PS of 3, 83% (1/8) for a 5PS of 4, and 67% (1/3) for a 5PS of 5 (P < 0·001). Patients with positive eoc‐PET‐CT scans who were selected for salvage RT alone had experienced a very good partial response to ABVD. Risk factors for recurrence in this subgroup included a small reduction in tumour size and a ‘bounce’ in ≥1 PET‐CT parameter (reduction then rise from interim to final scan). Thus, a positive eoc‐PET‐CT is associated with inferior FFP; however, appropriately selected patients can be cured with RT alone.     

Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) salvage of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP)-resistant advanced Hodgkin's disease

Thirty-nine patients with advanced Hodgkin's disease were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Thirty-one of these patients had previously failed to respond to MOPP (mechlorethamine, vincristine, prednisone, and procarbazine) treatment (29 patients) or to CCVPP (lomustine, cyclophosphamide, vincristine, procarbazine, and prednisone) treatment (two patients). Twenty-seven patients were considered evaluable: eight (30%) achieved complete remission (CR), two (7%) achieved partial remission (PR), and 17 (63%) had no response. All of the complete responders are still in continuous unmaintained CR, while 14 of the 19 partial responders and nonresponders have died. The overall median survival was 21 months; it was 16 months for partial responders and nonresponders. The remaining eight patients had ABVD substituted to MOPP early in treatment, because of allergy to procarbazine: six patients achieved CR and two achieved PR. Our results are in keeping with the literature data and confirm the effectiveness of ABVD as primary and salvage treatment in advanced Hodgkin's disease.     

Early and intermediate stage Hodgkin's lymphoma--report from the Swedish National Care Programme

In Sweden a National Care Programme provides treatment principles for Hodgkin's lymphoma (HL) since 1985, for early and intermediate stages often less extensive than international recommendations. The purpose is to evaluate long-term results of these principles. A total of 308 patients (167 men and 141 women), 17-59 yr old (median 31), diagnosed during 1985-92, pathological stage (PS) I-III1A and I-IIB and clinical stage (CS) I-IIA, mean follow-up 8.8 yr, were studied. Staging laparotomy was recommended in CS IIA. Recommended treatment was mantle or mini-mantle radiotherapy (RT) alone in CS IA, and PS I-IIA and subtotal nodal irradiation in PS III1A if the disease was not bulky. Patients in PS I-IIA and III1A with bulky disease, and PS I-IIB received one cycle of mechlorethamine, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, lacarbazine (MOPP/ABVD) before irradiation. The remaining patients received three to four cycles of MOPP/ABVD with RT to bulky disease. Relapse-free (RFS), Hodgkin specific (HLS), and overall survival (OS) at 10 yr were 74%, 92% and 85%. In the individual stages, RFS ranged from 53% (PSIII1A) to 90% (PS IA). RFS (P = 0.006), HLS, and OS were significantly better in patients treated with chemotherapy compared with those treated with RT alone, especially in patients with bulky disease (P = 0.0005). The international prognostic score did not provide any prognostic information. The OS rates are in agreement with results from international centres during that time. The recommended treatment was sufficient to produce the desired results of <20-30% recurrences, except in PS III1A. Most relapses could be salvaged. Patients with risk factors treated with one MOPP/ABVD and RT had an excellent outcome, superior to those without risk factors treated with RT alone. These results favour the trend to treat early and intermediate stages with a short course of chemotherapy followed by limited RT.     

Three cycles of adriamycin,bleomycin, vinblastine,and dacarbazine (ABVD) or epirubicin,bleomycin, vinblastine,and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial

From 1990 to 1996, a total of 386 adult patients with early/intermediate Hodgkin disease (HD) were randomly assigned to receive 3 cycles of adriamycin, bleomycin, vinblastine, dacarbazine (an alkylating agent), and methylprednisolone (ABVDm, arm A) or epirubicin, bleomycin, vinblastine, methotrexate, and methylprednisolone (EBVMm, arm E), a combination without alkylating agent. Responding patients received extended field radiation therapy (RT). Postchemotherapy complete remission and 10-year freedom from progression rates were higher in arm A (79.5% and 91.4%) than in arm E (70.4%, P =.04, and 80%, P <.002). HD mortality (HDM), treatment-related mortality (TRM), and overall survival (OS) were similar in both arms (A, 2.1%, 7.5%, and 90.4%; B, 3.9%, 5.5%, and 90.3%). However TRM and OS rates were lower in patients aged 40 years or older (P <.005), reflecting the increasing incidence of background fatal events with increasing age. Finally, event-free survival (EFS) was higher in arm A (84.6%) than in arm E (74.9%, P <.02). In patients aged younger than 40 years in arm A (74%), 10-year EFS and OS rates were 88.9% and 95.4% with HDM and TRM rates as low as 0.7% and 3%. Three courses of ABVDm plus RT are the best available option for treating early or intermediate HD.     

Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.     

A phase II study of dose‐dense and dose‐intense ABVD (ABVDDD‐DI) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma

We explored activity and safety of a dose‐dense/dose‐intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVD_DD‐DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two‐stage Bryant‐Day Phase II study to receive six cycles of ABVD_DD‐DI without consolidation radiotherapy. Cycles were supported with granulocyte colony‐stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m²; first four cycles only). Co‐primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event‐free (EFS) and disease‐free survival (DFS). All patients received the four doxorubicin‐intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose‐intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five‐year EFS and DFS was 88·3% and 93·7%, respectively. ABVD_DD‐DI regimen was well‐tolerated and ensured substantial CR and EFS rates without radiotherapy.     

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin��s lymphoma: a systematic review

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin’s lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin’s lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin’s lymphoma.     

G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis

Dose-intensity of chemotherapy is important in the treatment of Hodgkin lymphoma (HL) and granulocyte-colony stimulating factor (G-CSF) is commonly used to maintain it. We reviewed all newly diagnosed HL patients who were treated at our institution between 1996 and 2005. Fifty-nine patients received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose reductions, treatment delays, and without G-CSF, regardless of absolute neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was 0.925 x 10(9)/l, and was <0.5 x 10(9)/l on 26% of treatment days. Median normalised ABVD dose-intensity was 99.1% (range, 93-100%) and median cycle duration was 28.2 d. Incidence of bleomycin lung toxicity was 1.6%, 0.44% treatments were complicated by febrile neutropenia, and no secondary malignancies have occurred (median follow-up 48 months; range, 11-130 months). Five-year event-free (EFS) and overall survival (OS) were 92.9% and 97.4% respectively. Furthermore, the 5-year EFS and OS (87.4% and 94.1% respectively) for advanced stage patients compared favourably with a similar ABVD patient group who received routine prophylactic G-CSF (n = 23) with EFS 80.0% and OS 91.3% (P = 0.46 and 0.67 respectively). Our experience suggests that ABVD may be safely and effectively administered at >99% dose-intensity without G-CSF support, regardless of the ANC.     

Reduced intensity VEPEMB regimen compared with standard ABVD in elderly Hodgkin lymphoma patients: results from a randomized trial on behalf of the Fondazione Italiana Linfomi (FIL)

Survival rates for elderly Hodgkin Lymphoma (HL) have not improved substantially in recent years, mainly because of a lack of prospective randomized studies, due to difficulties in enrolling patients. Between 2002 and 2006, 54 untreated HL patients, aged between 65 and 80 years and considered ‘non‐frail’ according to a comprehensive geriatric evaluation, were enrolled into a phase III randomized trial to compare a reduced‐intensity regimen (vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone, bleomycin; VEPEMB) with standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Primary endpoint was progression‐free survival (PFS). Seventeen patients were in early stage (I‐IIA), while 37 were advanced stage. Median age was 72 years and median follow‐up was 76 months. Five‐year PFS rates were 48% vs. 70% [adjusted Hazard ratio (HR) = 2·19, 95% confidence interval (CI) = 0·94–5·10, P = 0·068] and 5‐year overall survival (OS) rates were 63% vs. 77% (adjusted HR = 1·67, 95% CI = 0·69–4·03, P = 0·254) for VEPEMB compared to ABVD. Overall treatment‐related mortality was 4%. World Health Organization grade 4 cardiac and lung toxicity occurred in four patients treated with ABVD versus no cases in the VEPEMB arm. Standard ABVD regimen resulted in better PFS and OS than the VEPEMB, although the differences were not statistically significant. The low toxicity of both treatments was probably attributable to stringent selection of patients based on a Comprehensive Geriatric Assessment that excluded frail patients.     

Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin's disease: results of the groupe d'études des lymphomes de l'Adulte H89 trial

The treatment of advanced Hodgkin's disease (HD) with chemotherapy (CTx) alone or combined modality treatments has been controversial. In 1989, we designed a randomized study to compare 2 cycles of CTx to (sub)total nodal irradiation (RTx) as consolidation treatments for patients with stage IIIB/IV HD in complete remission (CR) or good partial response after 6 cycles of CTx. A total of 559 patients were randomized to receive 6 cycles of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine) hybrid (n = 266) or ABVPP (n = 267). After induction treatment, 418 patients could be evaluated for the consolidation phase. With a median follow-up of 48 months, the 5-year disease-free survival estimates were 80% for 8 cycles of MOPP/ABV, 82% for 6 cycles of MOPP/ABV plus RTx, 68% for 8 cycles of ABVPP, and 75% for 6 cycles of ABVPP plus RTx (P =.01). The 5-year disease-free survival estimates did not differ between CTx and RTx, 74% and 79%, respectively (P =.07). After MOPP/ABV, the 5-year overall survival estimates did not differ between CTx and RTx, 85% and 88%, respectively (P =.2). After ABVPP, the 5-year survival estimates were 94% for CTx and 78% for RTx (P =.002). These results showed that RTx was not superior to CTx consolidation after doxorubicin-induced CR for patients with advanced HD. Because of the uncertainty of obtaining a prolonged second remission for patients relapsing after CTx and RTx and the possible long-term effects of RTx, we prefer 8 cycles of CTx as standard treatment when a CR has been achieved after 6 cycles.     

Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage IIBIV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) ‘CT-RT Group’ a=94 or RT alone, RT Group n=90. In the ‘CT-RT Group’, of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged>45 and those with Hb >10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p<0.01. In the ‘RT Group’ 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the ‘CT-RT Group’ and the ‘RT Group’ is 38%+2.01 (SE) and 36%+1.85 (SE), p=0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the ‘CT RT Group’ 29 patients responded; CR-8 (22.2%>), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT - 24 of 35 (68.6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the ‘RT Group’ - 21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71%> in the ‘CT-RT Group’ and 69% in the ‘RT Group’, p=ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity - two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.     

Comparative study of the efficacy of the DBVCy protocol (daunoblastin, bleomycin, vincristine, cytostasan) and the ABVD protocol in advanced Hodgkin's lymphoma. A prospective inter-clinic study within the framework of the Hauptforschungsrichtung Geschwulsterkrankungen

In MOPP-resistant patients with Hodgkin-lymphoma stage III B and IV the well known ABVD-protocol was compared with the DBVCy-protocol (daunorubicin, bleomycin, vincristine, cytostasan) in a randomized prospective trial. 73 patients were evaluable, 35 received ABVD, 38 DBVCy. 4 out of 35 (11%) in the ABVD-group and 9 out of 38(24%) in the DBVCy-group reached complete remission. The median duration of the remission for DBVCy was 4,5 months, for ABVD 3,4 months (no significance). Median survivals (61 months in DBVCy and 37 months in ABVD) did not show significant differences; but the DBVCy-scheme seems to be better tolerabel. With the given evaluation can not be proved a difference between the two groups, but it is not likely, that one of the regimen is very much better or very much worse as the other.     

ABVD chemotherapy for Hodgkin lymphoma at a single institute

Fifty-eight newly diagnosed patients with Hodgkin lymphoma were treated with ABVD chemotherapy at Yokohama City University Hematology group from October 1996 to June 2005. The median age of patients age was 41 years old and ranged from 15 to 75. Thirty-eight patients were in the early stage and 20 patients were in the advanced stage. Patients in the early stage received 3 cycles of ABVD chemotherapy and involved-field radiation therapy, while those in the advanced stage received 6 cycles of ABVD chemotherapy. The overall response rate in patients was 100% (CR 87%, PR 13%) in the early stage and 95% in the advanced stage. With a median follow-up of 44 months, the 3-year progression-free survival and overall survival were 89% and 95% in the early stage, and 70% and 81% in the advanced stage, respectively. The results of this study were similar to those previously reported in Western countries.     

ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis

We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT) (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2-82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results.     

Relapse and late complications in early-stage Hodgkin's disease patients with mediastinal involvement treated with radiotherapy alone or plus one cycle of ABVD.

BACKGROUND AND OBJECTIVE: Patients affected by Hodgkin's disease (HD) in pathologic stage IA-IIA have a strong possibility of remission and long-term survival when treated with radiotherapy to extended fields. However, 20-30% of cases relapse in the five years following treatment and consequently need further therapy. This study examines the occurrence of relapse and other complications in patients with pathologic stage IIA Hodgkin's disease and mediastinal involvement treated in different ways: radiotherapy alone vs radiotherapy plus one cycle of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). DESIGN AND METHODS: Our series consisted of 73 HD patients with mediastinal involvement treated by the Department of Radiation Oncology and the Hematology Department of "La Sapienza" University of Rome from 1983 to 1989. The patients were randomized into two groups according to their initial treatment. The first group contained 37 patients treated, initially, with supradiaphragmatic radiotherapy and para-aortic irradiation (STNI); the second group was made up of 36 patients treated, initially, with supradiaphragmatic radiotherapy and para-aortic irradiation (STNI) combined with one course of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). For 28 (38%) of the patients, the follow-up period was longer than 10 years. The average follow-up period was 114 months (range 22-174 months). Overall survival and relapse-free survival were assessed using the Kaplan and Meier method, while differences were tested by the log-rank test. RESULTS: We recorded twelve cases of relapse after initial treatment. The period of time which elapsed between the end of treatment and the evidence of relapse ranged from 6 to 51 months, with an average of 22 months. Ten relapses occurred in the STNI group and two in the ABVD/STNI group. No statistically significant differences emerged between the two groups in the overall survival analysis but did in the relapse-free survival analysis (p<0.01). In the group treated with ABVD and STNI one patient developed acute non-lymphocytic leukemia and another patient treated at the age of 44 developed primary breast cancer. X-ray-related asymptomatic pulmonary fibrosis was observed in 12 patients: 10 cases in the STNI and ABVD group and 2 cases in the group treated with RT alone. The other sequelae of combined CT/RT treatment in our study were thyroid dysfunction (2 cases, hypothyroidism), whereas the sequela of RT treatment was cardiac disease (2 cases). INTERPRETATION AND CONCLUSIONS: We conclude that one cycle of ABVD and radiotherapy in early-stage HD patients with mediastinal involvement may reduce the risk of relapse. Moreover, the combination of low-toxicity CT and RT, administered preferably to limited fields, in patients who have not undergone laparotomy could be a valid alternative to current treatment for early-stage HD. However, additional data and a longer follow-up are mandatory in order to evaluate late toxicity and the potential risk of treatment.     

The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis

To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2 induction cycles of daunorubicin and cytarabine with or without PSC-833. Patients in complete remission were then given 1 consolidation cycle without PSC-833. Neither complete response (CR) rate (54% versus 48%; P = .22), 5-year EFS (7% versus 8%; P = .53), disease-free survival (DFS; 13% versus 17%; P = .06) nor overall survival (OS; 10% in both arms; P = .52) were significantly improved in the PSC-833 arm. An integrated P-gp score (IPS) was determined based on P-gp function and P-gp expression in AML cells obtained prior to treatment. A higher IPS was associated with a significantly lower CR rate and worse EFS and OS. There was no significant interaction between IPS and treatment arm with respect to CR rate and survival, indicating also a lack of benefit of PSC-833 in P-gp-positive patients. The role of strategies aimed at inhibitory P-gp and other drug-resistance mechanisms continues to be defined in the treatment of patients with AML.     

ABVD第1、8天用药方案治疗初治霍奇金淋巴瘤疗效观察

目的 探讨阿霉素、博莱霉素、长春新碱、氮烯咪胺(ABVD)第1、8天用药方案治疗初治霍奇金淋巴瘤(HL)的疗效.方法 将我院2005年10月-2006年10月收治的Ⅱ～Ⅳ期初治HL62例患者,采用随机分组的方法将患者分为A、B两组,每组均为31例,A组采用ABVD第1、8天用药方案进行化疗6～8周期,B组采用ABVD第1、15天用药方案进行化疗6～8周期,两组患者化疗结束后均南同一位放疗科医生根据具体情况给予放疗,制定放疗方案不受A、B分组的影响.结果 A组化疗结束后完全缓解(CR)率90.3%(28/31),1年无病生存(DFS)率87.1%(27/31),2年DFS80.0%(20/25).B组化疗结束后CR 83.9%(26/31),1年DFS 80.6%(25/31),2年DFS 72.0%(18/25).A、B两组CR率、1年DFS率、2年DFS率比较,差异均无统计学意义(P>0.05).治疗相关的毒副反应,心肌缺血、Ⅲ～Ⅳ度肝功能损害、重度骨髓抑制等比较,差异无统计学意义(p>0.05).A组每例患者从化疗开始到化疗结束的平均时间为159 d,B组为228 d,A组较B组平均每人缩短69 d.结论 采用ABVD第1、8天用药方案治疗初治Ⅱ～Ⅳ期HL与第1、15天用药方案治疗CR率、1年DFS率、2年DFS率比较均相似,但A组有优于B组的趋势,治疗相关的毒副反应也相似,但在治疗时间上A组显著缩短.