Intermediate dose of intravenous melphalan in advanced multiple myeloma.

Eighteen patients with advanced multiple myeloma resistant to VAD chemotherapy (vincristine, Adriamycin, dexamethasone) were treated with intravenous melphalan in a single-pulse dose of 50-70 mg/m2. Objective response (greater than or equal to 50% reduction of the monoclonal protein) was observed in 9 patients. The median duration of remission in the responding patients was 6 months and the median survival 11.5 months. The main toxicity noted was bone marrow suppression. We conclude that intermediate doses of intravenous melphalan are a useful therapeutic modality in refractory or relapsing myeloma patients.     

Treatment approaches for relapsing and refractory multiple myeloma

Relapsing patients with multiple myeloma show a response rate higher than 50% with the resumption of the initial chemotherapy. However, since the duration of second responses are short, HDT/autotransplantation is recommended in patients with sensitive relapse. In patients with primary refractory myeloma the best treatment approach seems to be early HDT/autotransplantation. It is crucial to recognize a subset of patients who do not respond to the initial chemotherapy but who have non-progressive disease in order to avoid the administration of salvage regimens until clinical disease progression occurs. The treatment of patients with refractory relapse is disappointing. The most promising agent in this situation is thalidomide. Patients with late relapse after autologous transplantation can benefit from a second autologous transplant. The results of the allogeneic transplantation after autotransplantation are disappointing. In heavily pretreated resistant patients a conservative approach with alternate day prednisone (30 to 50 mg) along with pulse cyclophosphamide (800 to 1200 mg every 2 to 3 weeks) is recommended.     

Thalidomide in refractory and relapsing multiple myeloma.

Patients with multiple myeloma (MM) refractory to chemotherapy can only benefit from supportive measures and have a very short survival. Thalidomide has recently shown antitumor activity in patients with refractory myeloma. Twenty-three patients (12 men and 11 women; median age, 72 years) with advanced MM were treated with thalidomide. Sixteen patients had refractory disease and seven had untested relapse. The median dose of thalidomide was 400 mg d (range, 200 to 800 mg/d). The drug was generally administered in two divided doses. Five patients required treatment discontinuation because of toxicity. Twelve of 23 patients (52%) responded. Three (13%) achieved a partial response, with greater than 50% reduction in serum monoclonal (M)-protein levels, and nine (39%) attained a minimal response, with a greater than 25% decrease in serum M-protein levels. No decrease in the size of soft tissue plasmacytomas was observed in six patients with extramedullary involvement.     

A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients.

In order to assess the role of maintenance melphalan and prednisone (MP) in responding multiple myeloma patients, 185 eligible patients who responded to initial MP with stabilization for at least 4 months were randomized to either stop treatment and resume therapy at relapse or to continue MP until relapse. Time to first relapse was significantly shorter in the no maintenance group (P = 0.0011), however 57% of the no maintenance patients had a second response when MP was restarted and others had minor improvement. The time to final progression on MP, which reflects the duration of disease control by MP, was therefore longer for the no maintenance group (median = 39 months) compared to the maintenance group (median = 31 months) although the observed difference was not statistically significant (P = 0.086). Median survival from start of MP in the maintenance group (46 months) was also not significantly different than the no maintenance group (51 months) (P = 0.587). Multifactor analysis of the randomized patients demonstrated shorter total remission duration and shorter survival in patients who had an initially rapid response to therapy or a lesser reduction in serum M-protein concentration.     

FND方案治疗难治性、复发性多发性骨髓瘤的初步报告

背景与目的:多发性骨髓瘤(multiplemyeloma,MM)完全缓解率低、复发率高,绝大多数的MM患者经数个联合化疗方案后都会进入难治或复发阶段。本研究旨在观察含氟达拉滨(Fludarabine,Flu)的FND方案(Flu、米托蒽醌、地塞米松)治疗难治和复发性MM的疗效、毒副反应,以期为难治和复发性MM探索出安全有效的治疗方法。方法:将采用VAD方案(长春新碱、吡柔比星、地塞米松)化疗的22例患者作为历史对照组,观察和比较FND组(11例)和VAD组的疗效、达到缓解所需的时间,M蛋白下降50%以上、骨髓涂片中骨髓瘤细胞比例下降80%或占有<5%及血红蛋白上升20g/L的患者例数和时间,化疗后外周血白细胞和血小板的变化,治疗前后血钙、血肌酐、谷丙转氨酶的变化及不良反应。比较FND组治疗前后MM患者血清β2-微球蛋白的变化。结果:FND组的PR率是45.5%(5/11),高于VAD组的22.7%(5/22)(P<0.05),FND组达到PR的中位时间为76天,长于VAD组的68天(P<0.05)。M蛋白下降50%以上、血红蛋白上升20g/L在FND组分别为45.5%(5/11)、54.5%(6/11),均高于VAD组的22.7%(5/11)、18.2%(4/22)(P<0.05)。两组在治疗前后血钙、血肌酐、谷丙转氨酶均无明显变化;FND组治疗后MM患者血清β2-微球蛋白为(1042.8±72.3)μg/L,显著低于治疗前的(2350.2±184.0)μg/L(P<0.05)。FND组白细胞下降最低值为(0.9±0.5)×109/L,明显低于VAD组的白细胞下降的最低值[(2.1±0.6)×109/L](P<0.05);用FND方案治疗MM过程出现发热、咳嗽分别为36.4%(4/11)、45.5%(5/11),高于VAD组(分别为4.5%和9.0%)(P<0.05)。结论:用含Flu的FND方案治疗难治性、复发性多发性骨髓瘤PR率优于VAD组,但FND方案发挥明显疗效的时间较长,对骨髓的抑制较VAD方案显著,无肝肾毒性,是一种有效、安全的治疗难治性、复发性MM的方案。     

Newly diagnosed multiple myeloma

Opinion statement Melphalan combined with prednisone (MP) has been accepted as the standard therapy for previously untreated multiple myeloma (MM) because most studies demonstrate only a modest survival benefit of combination chemotherapy regimens when compared with MP. There have been modest gains with more intensive myeloablative regimens in combination with blood stem cell support, particularly for patients with early primary refractory disease who subsequently achieve partial remission, and for the approximately 25% to 35% of patients achieving complete remission. To preserve the ability to adequately collect stem cells, the use of alkylating agents, such as melphalan, should be limited in the previously untreated patient with myeloma (including those older than 65 years of age) who is a candidate for myeloablative therapy. Pulse dexamethasonecontaining regimens provide rapid responses and may be considered the first regimens of choice. Although vincristine/doxorubicin/dexamethasone (VAD) produces responses in approximately 50% to 70% of patients with previously untreated multiple myeloma, use early in the disease has not improved survival. Outside of a specific study protocol, this regimen may be best reserved for patients with refractory (particularly relapsing) disease. Notable exceptions include patients with renal failure or plasma cell leukemia in whom the rapid responses provided by VAD may avoid potentially permanent, serious complications. Recently, new agents with novel mechanisms of action (ie, thalidomide, immunomodulatory drugs, proteosome inhibitors) have demonstrated activity in resistant myeloma. Because these agents are likely to show activity alone or in combination, newly diagnosed patients and previously untreated patients should be considered for clinical trials. Thalidomide/dexamethasone has already produced response rates of 65% to 75% in previously untreated patients. Its ease of administration along with stem cell preservation are likely to make this, followed by myeloablative therapy with stem cell support, the treatment of choice for untreated myeloma as confirmatory studies are completed.     

Therapy of primary resistant and relapsed multiple myeloma

This article reports the efficacy of two salvage programs for primary resistant and relapsed multiple myeloma. Employing high dose dexamethasone alone or combined with continuous infusions of vincristine and adriamycin (VAD) in 83 patients, 1/3 achieved a greater than or equal to 75% tumor cytoreduction. The highest response rate of 65% was observed among previously responding patients receiving VAD compared to approximately 1/4 among those receiving VAD for primary resistant disease or dexamethasone alone regardless of prior response status. Tumor halving times were short with values of 0.5 months for VAD and 1.3 months for dexamethasone alone. The single most important pretreatment variable associated with failure to achieve remission was a low RNA content of myeloma plasma cells in the bone marrow. The second program evaluated high dose melphalan with or without autologous bone marrow transplantation in 23 patients resistant to VAD salvage treatment. Ten of 23 patients responded for at least 2 months, and 4 others had a comparable anti-tumor effect but died between 4-6 weeks from disseminated infection. Unlike the VAD regimen, responses occurred regardless of prior response or plasma cell RNA content, and tumor halving times were extremely short with a median of 0.3 months. With autologous bone marrow support, the higher melphalan dose (140 vs. 100 mg/m2) could be more safely administered to an older patient population (median of 63 vs. 44 years) with 1 of 7 vs 6 of 16 drug-related deaths in the absence of marrow support.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arsenic trioxide (trisenox) therapy for acute promyelocytic leukemia in the setting of hematopoietic stem cell transplantation

The relapse-free survival of patients with acute promyelocytic leukemia (APL) has significantly increased during the last decade. The introduction of all-trans retinoic acid (ATRA) doubled the survival of patients with this disease. However, despite ATRA and anthracycline-based chemotherapy, 12%-30% of patients will still relapse. Arsenic trioxide (ATO) has demonstrated efficacy and safety in patients with first and subsequent relapsed or refractory APL, regardless of the disease-free interval. Treatment of relapsed and refractory patients with this novel therapy produces complete remission in 87% of patients and molecular remission in 83%. Studies have documented the efficacy of autologous and allogeneic transplantation as salvage therapy in relapsed and refractory APL. The introduction of ATO into the treatment regimen for APL has stimulated discussion on its role in the transplantation setting. Investigators recently met to discuss the issue and make recommendations regarding ATO therapy in patients who are in their second or subsequent complete remission and are candidates for transplantation. This article describes the pivotal studies of this novel agent, discusses risk factor stratification for relapse in patients with APL, and proposes protocols for treatment incorporating ATO therapy. In addition, it describes scientific issues in ongoing and proposed clinical trials of ATO therapy for this disease.     

High-dose chemotherapy with autologous stem-cell support for germ cell tumors: a critical review

High-dose chemotherapy (HDC) with autologous stem-cell support (ASCS) has been investigated in patients with cisplatin-resistant, relapsed, or poor-prognosis germ cell tumor (GCT). Although some of these patients have benefited from this approach, it is unknown when best to administer such therapy. This review categorizes the HDC/ASCS trials into those performed as (1) salvage therapy for second or greater relapse, (2) salvage therapy for first relapse, and (3) first-line therapy. From the trials performed to date, earlier use of HDC/ASCS (first-line or salvage therapy in first relapse) achieved a higher durable remission rate than when used later as salvage therapy in second or greater relapse (approximately 50% v 15%, respectively). HDC/ASCS is not beneficial for relapsed or cisplatin-resistant primary extragonadal GCT patients, but may have a role in testicular GCT who are not "absolutely" cisplatin-resistant. Trial differences regarding the patients selected and the high-dose transplant preparative regimen used have made precise comparative analyses difficult. There has been only one phase III trial and it did not show a survival advantage to the HDC/ASCS arm, although this trial had significant methodological difficulties. In the future, more definitive treatment recommendations may be made upon completion of two ongoing phase III trials comparing HDC/ASCS with standard chemotherapy in the first salvage and front-line settings.     

VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.     

Salvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia

BackgroundThe prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is poor, with no universal standard salvage therapy currently available for most patients. Novel therapies with efficacy in patient subsets often have limited activity in alternative subsets, resulting in a majority of patients not gaining benefit from these therapies. This study systematically evaluated patient outcomes in a large cohort of R/R AML patients from a single institution across all salvage therapy lines, up to and including the third line.Patients and MethodsOutcomes of R/R AML patients treated at a single institution (MD Anderson Cancer Center, Houston, TX) between 2002 and 2016 were entered into a central database. Eligible patients received one or more lines of salvage therapy after first occurrence of R/R AML. Patients who received second- or third-line salvage treatment were also included in the first salvage analysis. Eligible patients were ≥ 18 years old at time of initial AML diagnosis, with no central nervous system involvement.ResultsA total of 818 eligible patients received one or more lines of salvage therapy, 809 received second-line salvage therapy, and 397 received third-line salvage therapy. Complete remission rates decreased from 14% after first salvage therapy to 9% after second salvage therapy and 3% after third salvage therapy. Median overall survival was 6.30, 4.07, and 2.98 months after first, second, and third salvage therapies, respectively.ConclusionThese data indicate that the best chance of obtaining long-term remission in AML is with a successful first induction. Strategies that improve initial response and decrease the likelihood of relapse should be pursued.     

Patterns of Relapse or Progression After Bortezomib-Based Salvage Therapy in Patients With Relapsed/Refractory Multiple Myeloma

IntroductionBortezomib-based therapy is commonly used in treatment for relapsed or refractory multiple myeloma (MM). Unfortunately, many patients show relapse or progression in heterogeneous patterns.Patients and MethodsIn this study, we retrospectively evaluated patterns of relapse or progression after bortezomib-based salvage therapy in patients with MM and analyzed prognostic significance according to patterns of relapse or progression. One hundred forty-eight patients were treated with bortezomib-based therapy between November 2004 and April 2012. Of these patients, 104 (70.3%) patients relapsed or progressed after bortezomib-based salvage therapy. We divided the patterns of relapse or progression to the 2 groups: (1) the isoform relapse or progression (group A) in 89 (85.6%) patients as disease findings at initiation of bortezomib-based therapy; and (2) transformed relapse or progression (group B) in 15 (14.4%) patients (plasmacytoma, n = 7; light chain escape, n = 6; and plasma cell leukemia, n = 2) different from initial disease findings.ResultsMedian overall survival in group A and group B were 32.7 months (95% confidence interval [CI], 21.3-44.1) and 10.7 months (95% CI, 2.0-19.4) (P < .001), respectively.ConclusionMM patients who relapsed or progressed as the transformed pattern for bortezomib-based salvage therapy have an extremely poor prognosis and might require new innovative approaches.     

Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia

Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterized by the absence of detectable M-protein in serum and urine. The presenting features of nonsecretory myeloma are similar to those in patients with a detectable M-protein, except for the absence of renal function impairment. The response to therapy and survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small band or no evident M-spike on serum electrophoresis and heavy light-chain proteinuria. Thus, IgD myeloma can be considered a variant of Bence Jones myeloma; the presence of the IgD M-protein and the predominance of the lambda light chain are the only distinctive features. The median survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of adverse biologic prognostic factors in patients with advanced aggressive myeloma is already present at diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, and renal failure. Treatment with a single alkylating agent plus prednisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamide and etoposide, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-dose therapy followed by stem cell rescue should be offered to affected patients.     

Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.

PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.     

改良VAD方案联合沙利度胺治疗多发性骨髓瘤

目的:观察改良VAD方案联合沙利度胺治疗多发性骨髓瘤的临床疗效和不良反应。方法:12例多发性骨髓瘤均采用改良VAD方案联合沙利度胺治疗。沙利度胺的起始剂量为100mg/天,每周增加100mg,直至剂量增加至300mg/天。28天为1周期。治疗2个周期后,根据血象、血清M蛋白、血清肌酐、骨髓瘤细胞等指标来判断疗效,分为部分缓解、改善和无效。结果:部分缓解6例,改善4例,总有效率为83·3%。主要不良反应有嗜睡(75%)、便秘(50%)、头晕(25%)和感染(25%),但都能耐受。结论:改良VAD方案联合沙利度胺治疗多发性骨髓瘤具有疗效高和耐受性好的优点,尤其是对于有合并症的老年患者是安全的,值得进一步的临床观察和推广。     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

 目的　观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　35例初治及难治复发MM患者,硼替佐米1.1 mg／m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg／d开始逐渐加量至150 mg／d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案。28 d为1个疗程,每例患者至少接受2个疗程以上治疗。达到部分缓解（PR）及以上疗效的患者应用沙利度胺150 mg／d或患者能够耐受的最大剂量维持治疗。采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应。结果　中位随访20个月,35例患者治疗总有效率82.8 ％,其中完全缓解（CR）率48.6 %,良好的部分缓解（VGPR ）率17.1 %,PR率17.1 %。3年预计无进展生存（PFS）和总生存（OS）率分别为60.92 %和72.41 %。达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义（P＝0.004）。初治及难治复发患者客观缓解率（ORR）及OS率差异无统计学意义。Ⅲ～Ⅳ度非血液学毒性主要包括乏力（3／35）、恶心、呕吐（8／35）、便秘（4／35）和周围神经病变（3／35）。Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏（10／35）和血小板减少（8／35）。结论　低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间。     

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.     

Low dose thalidomide in patients with relapsed or refractory multiple myeloma

Remarkable results of the treatment of refractory multiple myeloma with thalidomide have been reported. In most preceding studies, the given thalidomide dose was escalated to a maximum tolerated dose of up to 800 mg/d. The frequency of adverse effects correlates with dose intensity. Since a significant gain of therapeutic effects could not be observed as thalidomide dosage was escalated, the optimal dose of thalidomide remains to be determined. We report the results of a study with low dose thalidomide (median administered dose 100 mg/d, range 50-400 mg/d). Twenty-four relapsed (n=19) or resistant (n=5) multiple myeloma patients were included in the study. Twelve patients (50%) received thalidomide as monotherapy, 8 patients (33%) received a combination of thalidomide and dexamethasone (every 4 weeks 40 mg/day for 4 days) and 4 patients (17%) who were resistant to vincristine, doxorubicin, dexamethasone (VAD) received VAD combined with thalidomide. Overall, a response was observed in 12 patients (50%). Of the 12 patients treated with low dose thalidomide alone 5 (42%) responded, of the 8 patients who received a combination of thalidomide and dexamethasone 5 (63%) responded and of the 4 patients who had thalidomide in addition to VAD 2 patients (50%) responded. In 3 patients, thalidomide treatment had to be discontinued because of side effects and 1 patient died before response could be assessed. We conclude that low dose thalidomide is an effective and safe rescue therapy in relapsing or refractory multiple myeloma. Response to thalidomide might be dependent on prognostic parameters and tumor burden. To answer these questions larger prospective studies are necessary.     

Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program

BACKGROUND: Despite recent advances in systemic and supportive therapies, multiple myeloma remains an incurable plasma cell malignancy. Novel therapeutic approaches are thus needed. Thalidomide has recently been recognized as an effective new agent for previously untreated, refractory or relapsed myeloma. PATIENTS AND METHODS: To evaluate the efficacy and tolerability of thalidomide in myeloma, we performed a retrospective analysis of 21 consecutive patients receiving thalidomide alone or in combination with dexamethasone and/or intermittent cyclophosphamide as first-line, maintenance or salvage therapy within a compassionate use program. RESULTS: Of the 21 patients, 16 (76.2%) had refractory or relapsed disease, including 7 (33.3%) patients relapsing after autologous stem cell transplantation. Three patients received thalidomide as maintenance therapy after having achieved a partial remission following autologous stem cell transplantation or conventional chemotherapy. Two patients were given thalidomide as first-line treatment for indolent disease. During long-term treatment (median 12 months, range 1-27 months), patients tolerated only low doses of thalidomide (50-150 mg/day) due to cumulative neurotoxicity. At a median follow-up of 16 months (range 1.5-28 months), we observed an overall response rate of 61.9% (50% for the subgroup receiving thalidomide alone; 77.8% for combination therapy) consisting of 1 complete response, 2 near-complete responses, 8 partial responses and 2 minor responses. Median progression-free survival was 20 months. CONCLUSIONS: We conclude that low-dose thalidomide (50-100 mg/day) alone or in combination is a safe, well-tolerated and effective form of therapy for patients with myeloma at various stages of disease.     

Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience).

BACKGROUND: The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone (MOPP) had failed. PATIENTS AND METHODS: From January 1982 to December 1989 among 210 patients treated with MOPP and radiotherapy to initial bulky sites, 65 patients were primary refractory to or relapsed after initial treatment. RESULTS: Twenty-nine of 65 patients (44%) were primary refractory to initial chemotherapy, 20 relapsed within 12 months after complete remission (CR) and 16 relapsed after CR that lasted more than 12 months. Patients with primary refractory HD and early relapse (<12 months after CR) were treated with doxorubicin/bleomycin/vinblastine/darcarbazine. In patients with late relapse (>12 months after CR) MOPP was repeated. The median follow-up for all patients was 115 months. The overall response rate was 63%. Thirty-three patients (51%) achieved a second CR and eight patients (12%) partial response. Remission rate was greatest in patients with late relapse (CR >12 months) (75 versus 55% for early relapse versus 35% for primary refractory HD) (P <0.01). At 10 years, overall and failure-free survival rates were 21 and 16%, respectively. Patients who were in first remission longer than 12 months had a superior overall survival (37 versus 18% for early relapse) and failure-free survival (24 versus 10% for early relapse). No patient with primary refractory HD was alive beyond 52 months after initial treatment failure (P <0.01). Main prognostic factors were duration of the first remission and tumor bulk at relapse. CONCLUSIONS: Our results confirm previous observations that a significant proportion of patients with HD who experience induction treatment failure cannot be cured with conventional treatment and probably need more aggressive therapy.