Mini-beam as salvage chemotherapy for refractory Hodgkin's disease and non-Hodgkin's lymphoma

Long-term disease-free survival after conventional dose salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) is rare. Intensive chemotherapy and autologous bone marrow transplantation (ABMT) is regarded by many as the treatment of choice. For lymphoma, eligibility for transplant is frequently restricted to cases with chemotherapy-sensitive disease or minimal tumour bulk. We evaluated the mini-BEAM regimen as further treatment for patients unresponsive to initial salvage therapy and thus ineligible for ABMT at our centre. Carmustine 60 mg/m(2) I.V. day one, etoposide 75 mg/m(2) I.V. days 2-5, cytosine arabinoside 100 mg/m(2) I.V. q12h days 2-5 and melphalan 30 mg/m(2) day 6 (mini-BEAM) was administered to 24 patients with lymphoma, 22 of whom were refractory to at least first-line salvage chemotherapy. Eleven had HD and 13 NHL. The complete response (CR) rate was 21% and the overall response was 59%. Febrile neutropenia occurred in 48% of treatment episodes. There were two treatment-related deaths. Thirteen patients underwent bone marrow transplantation (BMT), 11 received ABMT (8 HD, 3 NHL). Six patients did not achieve remission after transplant but 7 patients remain in continuous CR, with a follow-up of 6-17 months post-transplant. Consequently, 7 of 24 (29%) patients responded to mini-BEAM and many achieve long-term disease-free survival after BMT. Further evaluation of mini-BEAM as a salvage regimen prior to BMT is indicated.     

Outcome of Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma Referred for Autologous Bone Marrow Transplantation

Fifty-one patients with relapsed or refractory intermediate- or high-grade non-Hodgkin's lymphoma were referred for autologous bone marrow transplantation (ABMT). The primary criterion for eligibility was sensitivity to conventional-dose salvage chemotherapy. Of 47 patients who received salvage chemotherapy, 30 demonstrated chemotherapy-sensitive disease. Six eligible patients did not undergo ABMT for various reasons. A total of 24 patients underwent ABMT, with etoposide, melphalan ± total body irradiation as the intensive therapy regimen. There was one early treatment-related death and three non-responders. Of the remaining patients, 9 relapsed, while 11 remain in continuous complete remission (CR) at a median follow-up of 21 months after transplant (range 5-37 months). Two patients with chemosensitive disease and bone marrow involvement underwent allogeneic BMT with marrow from HLA-identical siblings. Both are in continuous CR at 6 and 12 months follow-up. Of the 25 patients who did not undergo ABMT, all have died (median survival 5 months).

The results indicate that approximately one-half of relapsed or refractory aggressive histology lymphoma patients referred for ABMT eventually undergo transplantation, if chemotherapy-sensitive relapse is the major criterion for eligibility. Approximately 25% of the referred patients may become long-term disease-free survivors with this approach. Reports of marrow transplant series should include all patients referred for ABMT as the denominator for calculating disease-free survival in order to reduce the bias of patient selection.     

The optimal timing of autologous bone marrow transplantation in Hodgkin's disease patients after a chemotherapy relapse.

PURPOSE: The optimal sequence of salvage chemotherapy (SC) and autologous bone marrow transplantation (ABMT) for Hodgkin's disease (HD) patients who relapse after primary chemotherapy is unknown. We created a decision analysis model to determine the optimal treatment strategy and the most cost-effective approach. METHODS: The decision tree simulated a 25-year-old HD patient who relapsed less than 12 months after mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy. Four strategies used ABMT in some sequence with SC; the final strategy considered SC alone. Clinical data were derived from 17 published reports chosen by explicit criteria. Costs of care were estimated from the published literature and institutional experience. RESULTS: The optimal strategy was ABMT in second relapse, which was superior to the SC-only option by 1.9 years at an incremental cost of $26,200 per each year of life saved. When the probabilities of complete remission and disease-free survival were reduced for SC, similar to the clinical expectation of SC after a seven- or eight-drug regimen like MOPP/doxorubicin, bleomycin, and vinblastine with or without dacarbazine (MOPP/ABV[D]), ABMT in first relapse was the preferred strategy and provided 6 additional months. However, when the data from favorable (or unfavorable) SC and ABMT reports were compared head-to-head in this model, SC followed by ABMT in second relapse was always optimal. CONCLUSIONS: All relapsed HD patients should plan to use ABMT in some sequence with SC, if necessary. In most situations the optimal strategy is ABMT in second relapse. This analysis will assist clinicians in planning treatment for relapsed HD patients. It could be refined if historical series were updated to report the incidence and outcomes of SC relapse from seven- or eight-drug regimens.     

Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dexa-BEAM)

Background: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT.Patients and methods: Twenty-six patients (median age 30, range 20–40 years) were treated with 2–4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide).Results: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continous CR (median follow-up 40 months, range 14–60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2–4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death.Conclusion: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.     

Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma

Background: High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and Methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin's disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III-IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.     

Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation

Background: The role of intensive chemotherapy with autologous blood andmarrow transplantation (ABMT) for patients with relapsed or refractoryintermediate grade non-Hodgkins lymphoma has recently been established.However, conventional dose salvage chemotherapy is frequently used todetermine chemotherapy sensitivity and reduce tumor bulk prior to intensivetherapy. Different salvage regimens have been proposed but none appearssignificantly superior. The purpose of this study was to determine theefficacy of mini-BEAM salvage chemotherapy in patients referred for ABMT andto define prognostic factors of response.Patients and methods: One hundred four patients referred forconsideration of ABMT after failure of primary anthracycline-basedchemotherapy received BCNU 60 mg/m² day 1, etoposide 75mg/m² day 2–5, ara-C 100 mg/m² q12h day2–5, melphalan 30 mg/m² day 6 (mini-BEAM) until maximumtumor reduction. Median age was 52 (range 18–65); 57% had failedto achieve a complete response (CR) to doxorubicin-based chemotherapy atdiagnosis and only 13% had a previous CR lasting > 12 months.Seventy-six received mini-BEAM as first salvage chemotherapy.Results: The overall response rate (RR) was 37% (95%confidence interval (CI) 28–46%) with 12 patients achieving CRand 25 achieving PR. Theresponse rate among patients treated as first salvage was 43% comparedto 20% for patients who had failed to respond to a previous salvageregimen. Only 15% of patients who failed to respond to mini-BEAMresponded to another conventional dose salvage regimen. Thirty-eight of 104patients ultimately demonstrated sufficient response to proceed to ABMT.Actuarial survival at four years is 22% for all 104 patients, and36% for those who went on to ABMT. For those who were not transplanted,four-year survival was 18%. B symptoms and tumor burden at relapse weresignificant predictors of response to mini-BEAM in multivariate analysis, andidentified a poor prognosis group of patients unlikely to be cured by thisapproach.Conclusions: Mini-BEAM does not appear to be a superior salvage regimen inthis high-risk group of relapsed or refractory NHL patients for whom ABMT wasthe ultimate treatment intention. Only one-third of patients referred for ABMTultimately proceed to transplant; alternative treatment strategies should bedeveloped for those with a low likelihood of cure by this approach.     

Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma

BACKGROUND:: Patients with Hodgkin's disease (HD) and intermediate or high-gradenon-Hodgkin's lymphoma (NHL) who fail to achieve a completeremission (CR) with standard induction therapy have a poor prognosiswith conventional-dose salvage therapy alone. We examined therole of subsequent intensive therapy and autologous bone marrowtransplantation (ABMT) in patients who demonstrated a responseto conventional-dose salvage therapy. PATIENTS AND METHODS:: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwentintensive therapy with etoposide (60 mg/kg), intravenous melphalan(160–180 mg/m²) followed by infusion of unpurged autologousbone marrow and/or blood cells. All patients had advanced stageor bulky disease at diagnosis and failed to achieve a CR afteran anthracycline-containing front-line chemotherapy regimen(NHL) or ABVD or equivalent regimen (HD). Patients who achieveda CR after involved-field radiotherapy were excluded. All patientsdemonstrated sensitivity to conventionaldose salvage treatmentbefore advancing to intensive therapy and ABMT. RESULTS:: The CR, partial response (PR) and overall response rate (RR)following ABMT for HD patients was 48%, 17% and 65%, respectively.At a median follow-up of 35 months, the predicted three-yearoverall survival (OS) is 51% (95% CI: 44%–60%) and event-freesurvival (EFS) is 34% (95% CI: 26%–54%). For patientswith NHL, the CR, PR and RR were 68%, 9% and 77%, respectively.At a median follow-up of 28 months, the predicted three-yearOS is 51% (95% CI: 35%–66%) and EFS is 39%(95% CI: 21%–57%). CONCLUSIONS:: Intensive therapy with etoposide and melphalan followed by ABMTresults in prolonged survival in selected patients with lymphomawho fail to achieve a complete remission to front-line chemotherapy.Based on our previous studies of outcome to conventionaldosesalvage chemotherapy, we estimate that of all patients failinginduction therapy, 28% with HD and 15% with NHL will be eventfreeat three years after ABMT. induction failure, Hodglun's disease, non-Hodgkin's lymphoma, refractory lymphoma     

A Single-Center Study of 11 Patients with Intraocular Lymphoma Treated with Conventional Chemotherapy Followed by High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in 5 Cases

Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m² as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m² IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT.

First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.     

Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.

PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.     

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.     

Current status of autologous stem cell transplantation in relapsed and refractory Hodgkin's lymphoma

Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, ～20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of ～50%-60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas.     

Salvage Therapy in Hodgkin's Lymphoma

Hodgkin's lymphoma (HL) is a commonly cured malignancy. Unfortunately, patients who are refractory to or relapse after first‐line treatment pose a significant therapeutic challenge. There is evidence that these patients are best treated with an approach involving salvage chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). This approach may result in cure, with better results in patients with low‐risk relapse. In patients with high‐risk relapse and refractory disease, HDCT/ASCT is rarely curative. More aggressive transplant approaches have shown promising results in this group and are currently under active investigation. For those relapsing after HDCT/ASCT, there exists a range of therapeutic options, including further salvage chemotherapy, reduced‐intensity allogeneic transplantation, monoclonal antibody therapy, and novel agents. All patients in this category should be considered for enrollment in clinical trials. This review discusses the evidence behind the current practice in patients with relapsed or refractory HL. Specifically, the efficacy of various salvage chemotherapy regimens, the risk factors influencing outcome with HDCT/ASCT, and the results with alternative transplant approaches, monoclonal antibody therapies, and novel agents are addressed. We conclude by providing our approach to these patients, with the hope that this will serve as a framework for the practicing oncologist.     

Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen.

PURPOSE: Of the 737 patients with aggressive lymphoma who were treated with the LNH-84 regimen, 244 with progressive disease after complete remission or partial response were analyzed retrospectively to determine the influence of intensive chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND METHODS: Forty-four patients were treated with salvage chemotherapy, followed by autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four. The other 200 patients were treated with chemotherapy only. RESULTS: Salvage treatment produced an objective response in 57% of the patients; 23% achieved a second complete remission. Median overall survival was longer for patients who were treated with ABMT than for those who were treated with chemotherapy only (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v 4 months). In multiparametric analysis, ABMT and normal initial lactic dehydrogenase (LDH) level were the primary parameters associated with longer survival. This is also true when (1) only patients younger than 60 years of age, (2) only patients who responded to salvage regimen, or (3) only patients with both conditions were included in the analysis. Patients who were not transplanted had a 1.69 to 2.26 relative risk of dying from their disease compared with those who were treated with intensive chemotherapy plus ABMT. CONCLUSION: This study produced more evidence of the favorable impact of intensive chemotherapy with bone marrow rescue on survival in lymphoma patients who had relapsed.     

A Pilot Study of Autologous Bone Marrow Transplantation Followed by Recombinant Interleukin-2 in Malignant Lymphomas

In this study, we investigated the impact of recombinant interleukin-2 (rIL-2) after high dose chemotherapy and autologous bone marrow transplantation (ABMT) in 25 patients with refractory or relapsed Hodgkin's disease (HD) (11 patients) and non Hodgkin's lymphoma (NHL) (14 patients). 48% of patients had resistant disease, 84% achieved complete remission after ABMT. rIL-2 was started at a median of 54 days post-transplant and consisted of a first cycle of 5 days followed by 4 cycles of 2 days every other week. Patients received a mean of 160 × 10⁶ IU/m² rIL-2 and hematological toxicity was moderate and transient. None of the 5 evaluable patients with measurable disease responded to rIL-2. After a 5 year median follow-up, the probability of survival and DFS is 72% (HD: 73% and NHL: 70%, p = NS) and 45% (HD: 36% and NHL: 48%, p = NS) respectively. These somewhat encouraging results warrant further evaluation of rIL-2 after ABMT in controlled studies, especially in NHL patients stratified for previous chemosensitivity.     

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: Cost, safety, and long-term efficacy

Background: Few data are available on the cost, safety, and long-termefficacy of single agent high-dose melphalan (HDM) followed by autologousbone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvagetherapy of Hodgkins disease (HD).Patients and methods: From February 1981 to September 1996, 23 patientswith relapsed (n = 15) or refractory (n = 8) HD received salvage therapywith HDM 140–200 mg/m² followed by non-cryopreservedABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996,from initial consultation until transfer back to referring physician, wasdetermined and compared to the estimated costs of two multi-agent regimenscommonly used for HD.Results: HDM was well tolerated with no early transplant-relatedmortality. The five-year overall and progression-free survival rates were52% and 50%, respectively. The average total cost in Canadianfunds of HDM/ABSCT in 1996 was $34,400/patient. This cost wasestimated to be $4,700–6,800 cheaper per patient than themulti-agent high-dose regimens.Conclusion: These data suggest that HDM is safe, feasible, active, andreasonably inexpensive salvage therapy for patients with relapsed/refractoryHD.     

耐药和复发的何杰金氏病化疗中剂量强度与疗效关系的分析

 耐药和复发的何杰金氏病（HD）是否该作自体骨髓移值（ABMT）仍是颇有争议的问题。剂量强度与疗效的关系是ABMT的理论基础。本文研究了1982～1994年间有关HD挽救化疗资料中的剂量强度与疗效关系，没有得出所希望的结论。但常规化疗的结果并不满意，Ⅲ线方案的CR率仅23%。ABMT在Ⅱ线方案失败的患者中有很强适应症。     

Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum) plus granulocyte colony-stimulating factor in patients with relapsed Hodgkin's disease

High-dose chemotherapy followed by autologous stem cell transplantation can improve the outcome of relapsed and refractory Hodgkin's disease (HD) patients. The objective of the trial was to determine the mobilizing potential of the DHAP salvage regimen (dexamethasone, cytarabine, cisplatin) for the collection of peripheral blood stem cells (PBSC) in patients with relapsed HD. The target yield of harvesting CD34 + cells was ≥ 2 × 10⁶/kg in order to support the subsequent myeloablative chemotherapy. Most of the 105 patients included were intensively pre-treated with different combination chemotherapy regimens prior to mobilization. The use of DHAP followed by granulocyte colony-stimulating factor (G-CSF; 10 μg/kg) resulted in the successful collection of adequate numbers of PBSC in 97.1% of patients (102 of 105) with a median harvest of CD34 + cells of 13 × 10⁶/kg (range 2.6 - 85.1). More than 2.0 × 10⁶ CD34 + cells/kg were achieved in 65 of 103 (63%) patients after 1 apheresis, the maximum number of aphereses for all patients was 3. It was found that the optimal time of PBSC harvest was at days 13 - 16 after initiating the mobilization regimen.

These results demonstrate that the salvage chemotherapy regimen, such as DHAP combined with G-CSF, can be successfully used to mobilize PBSC in HD patients.     

Salvage radiotherapy in recurrent Hodgkin's disease.

Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year.     

Brentuximab Vedotin in Transplant‐Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients

Background.

Hodgkin lymphoma (HL) is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. Approximately 30%–40% of patients with advanced disease are refractory to frontline therapy or will relapse after first-line treatment. The standard management of these patients is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT). The best prognostic factor is the status of disease before ASCT; in particular, the normalization of positron emission tomography (PET) scan. Brentuximab vedotin (BV) has shown a high overall response rate in refractory/relapsed HL after ASCT, whereas few data are available regarding its role before ASCT.

Patients and Methods.

A multicenter, retrospective, observational study was conducted. The primary endpoint of the study was the effectiveness of BV as single agent in patients with relapsed/refractory, ASCT-naïve HL, determined by the conversion of PET status from positive to negative; secondary endpoints were safety, capacity to proceed to ASCT, survival, and progression-free status.

Results.

Thirty patients with relapsed/refractory HL- and PET-positive disease after conventional chemotherapy salvage treatments were treated with a median of 4 cycles of BV. Normalization of PET findings (Deauville score ≤2) occurred in 9 of 30 patients (30%). Those nine patients proceeded to ASCT.

Conclusion.

These data suggest that BV can normalize PET status in a subset of HL patients refractory to conventional chemotherapy salvage treatments, such as ifosfamide-containing regimens, cytarabine- and platinum-containing regimens, prior to ASCT.

Implications for Practice:

Administration of brentuximab vedotin has resulted in a high overall response rate in refractory/relapsed Hodgkin lymphoma after autologous stem cell transplant, whereas few data are available regarding its role before transplant. The data suggest that brentuximab vedotin can normalize positron emission tomography results in a subset of patients refractory to conventional salvage treatments prior to transplant. Experience indicates that patients previously regarded as not ideal candidates for transplantation may be able to undergo further cytoreductive therapy using brentuximab vedotin.     

Allogeneic haematopoietic stem cell transplantation as a salvage strategy for relapsed or refractory nasal NK/T-cell lymphoma

Nasal NK/T-cell lymphoma is rare and occurs most frequently in East Asia and Latin America. It is characterized by its aggressive nature and tends to become resistant to chemotherapy and radiotherapy. Autologous haematopoietic stem cell transplantation (auto-HSCT) is often associated with a high relapse rate for the active or disseminated disease. There are limited data about allogeneic haematopoietic stem cell transplantation (allo-HSCT) for relapsed or refractory nasal NK/T-cell lymphoma. In our study, two patients with nasal NK/T-cell lymphoma were successfully treated with allo-HSCT. The first patient was a 31-year-old woman who relapsed after auto-HSCT. Subsequently, HLA-matched allo-HSCT was considered as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/Vm26/Ara-C. Donor lymphocyte infusion was used to reduce the risk of relapse. After allo-HSCT, the tumor in her nasal cavity gradually disappeared. She has been in continuous complete remission (CR) for 3 years. The second patient was a 26-year-old woman diagnosed with stage IIIB advanced nasal NK/T-cell lymphoma who was resistant to combination radiochemotherapy. She underwent HLA-matched allo-HSCT as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/MeCCNu/Ara-C. She has been in continuous CR for five years. The stem cell source was peripheral blood for both patients, and there was no severe graft-versus-host disease in either patient. Our clinical experience suggests that allo-HSCT with a modified conditioning regimen is a promising treatment for patients with relapsed or refractory nasal NK/T-cell lymphoma.