Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Safety and efficacy of mechanical thrombectomy with stent-retrievers in anticoagulated patients with anterior circulation stroke.

AIM: To assess the safety and efficacy of mechanical thrombectomy (MT) with stent-retrievers in anterior circulation stroke (ACS) patients due to the occlusion of major cerebral arteries, and to compare the results achieved in patients on oral anticoagulation (OAC) and those not on OAC. MATERIALS AND METHODS: The present retrospective study comprised 285 consecutive patients (115 males; mean age 74±13 years). The following data were collected: baseline characteristics, occurrence of risk factors, pre-event treatment with OAC, neurological deficit at the time of treatment, time to therapy, recanalisation rate (successful recanalisation defined as Thrombolysis in Cerebral Infarction score ≥2b), post-treatment imaging findings. The 90-day clinical outcome was assessed using modified Rankin scale (good outcome defined as 0-2). RESULTS: The following statistically insignificant differences were found in 26 patients on OAC versus 259 patients without OAC: occurrence of symptomatic intracerebral haemorrhage 7.7% versus 8.1%, achievement of successful recanalisation 69.2% versus 82.6%, good 90-day clinical outcome 34.6% versus 56.8%, 90-day mortality 26.9% versus 20.8% (p>0.05 in all cases). Age and neurological deficit at the time of treatment were identified as independent negative predictors of good 90-day clinical outcome (odds ratio [OR]=0.90, 95% confidence interval [CI]: 0.88-0.94 and OR=0.83, 95% CI: 0.77-0.90, respectively) and as independent positive predictors of mortality (OR=1.12, 95% CI: 1.06-1.18 and, OR=1.17, 95% CI: 1.07-1.27, respectively; p<0.05 in all cases). CONCLUSIONS: MT with stent-retrievers is safe and effective in ACS patients on OAC.

Correction to: Multidisciplinary approach in the treatment of spinal dural arteriovenous fistula-results of endovascular and surgical treatment.

The author J. Adamkov was incorrectly captured in the original article and is now corrected in this article.

Multidisciplinary approach in the treatment of spinal dural arteriovenous fistula-results of endovascular and surgical treatment.

BACKGROUND: The results of treatment for spinal dural arteriovenous fistula (SDAVF) have been controversial. The goal of this study was to compare results of endovascular and surgical treatments to contribute to determining an optimal treatment strategy. METHODS: A retrospective analysis of the set of 24 SDAVF patients (11 in the endovascular and 13 in the surgical group) was performed. The clinical effect (using the modified Rankin scale [mRS]), the radicality, and the number of clinical recurrences as well as the impact of age, the level of impairment, and the duration of symptoms before the treatment were evaluated. RESULTS: The average age was 60.1 ± 8.4 years. The median duration of symptoms before establishing a diagnosis was 12 (1-70) months. Clinical improvement was reported in 11 out of 24 (45.8%) patients (36.4% following embolization and 53.8% following surgery, p = 0.444). Radical performance was achieved in 47.4% of endovascular versus 92.9% of surgical procedures (p = 0.009). Clinical recurrence was reported in 35.3% of patients in the endovascular group, whereas no clinical recurrence was reported in the surgical group (p = 0.0133). The graphical residuum after 1 surgery out of 14 (7.1%) was cured early during the control angiography. Clinical improvement was reported 42.1% of patients with mRS ≤ 3 versus 60% of patients with mRS ≥ 4 and, in 57.1% of patients aged ≥ 60 versus in 30% of patients < 60 years (p > 0.05 in both cases). The impact of the duration of symptoms on the clinical results was not statistically significant. CONCLUSIONS: The surgical treatment of SDAVF appeared to be a more efficient method in terms of the clinical effect, radicality, and lower recurrence rate in comparison with the endovascular treatment. No statistically significant dependence of the clinical result on age, deficit burden, or symptom duration was found.

Transcranial Sonography of the Insula: Digitized Image Analysis of Fusion Images with Magnetic Resonance.

Purpose: Transcranial B-mode sonography (TCS) of brain parenchyma is increasingly used as a diagnostic tool for movement disorders. Accordingly, experimental B-Mode Assist software was developed to enable digitized analysis of the echogenicity of predefined brain regions. The aim of the study was to assess the reproducibility of digitized TCS image analysis of the insula. Materials and Methods: A total of 130 patients with an indication for neurosonological examination were screened for participation in the study. The insula was imaged from the right temporal bone window using Virtual Navigator and TCS-MRI (magnetic resonance imaging) fusion imaging. All subjects were examined three times by two experienced sonographers. Corresponding images of the insula in the axial thalamic plane were encoded and digitally analyzed. Interclass correlation coefficient (ICC) and Spearman's rank correlation coefficient were used for the assessment of intra- and inter-reader as well as intra- and inter-investigator reliabilities. Results: TCS images of 114 patients were evaluated (21 patients with TIA, 53 patients with headache, 18 patients with essential tremor, 22 patients with neurodegerative disease). 16 patients were excluded from analysis due to insufficient bone window. The intra-reader, inter-reader, intra-investigator and inter-investigator ICCs/Spearman's rank correlation coefficients were 0.995/0.993, 0.937/0.921, 0.969/0.961 and 0.875/0.858, resp. Conclusion: The present study demonstrates a high reliability to reproduce echogenicity values of the insula using digitized image analysis and TCS-MRI fusion images with almost perfect intra-reader, inter-reader, intra-investigator and inter-investigator agreement.

Inoculation methods using Rhodococcus erythropolis strain P30 affects bacterial assisted phytoextraction capacity of Nicotiana tabacum.

In this study different bacterial inoculation methods were tested for tobacco plants growing in a mine-soil contaminated with Pb, Zn, and Cd. The inoculation methods evaluated were: seed inoculation, soil inoculation, dual soil inoculation event, and seed+soil inoculation. Each inoculum was added at two bacterial densities (10(6) CFUs mL(-1) and 10(8) CFUs mL(-1)). The objectives were to evaluate whether or not the mode of inoculation or the number of applied microorganisms influences plant response. The most pronounced bacterial-induced effect was found for biomass production, and the soil inoculation treatment (using 10(6) CFUs mL(-1)) led to the highest increase in shoot dry weight yield (up to 45%). Bacterial-induced effects on shoot metal concentrations were less pronounced; although a positive effect was found on shoot Pb concentration when using 10(8) CFUs mL(-1) in the soil inoculation (29% increase) and in the seed+soil inoculation (34% increase). Also shoot Zn concentration increased by 24% after seed inoculation with 10(6) CFUs mL(-1). The best effects on the total metal yield were not correlated with an increasing number of inoculated bacteria. In fact the best results were found after a single soil inoculation using the lower cellular density of 10(6) CFUs mL(-1).

Randomized clinical trial comparing neurological outcomes after carotid endarterectomy or stenting.

BACKGROUND: Silent infarction in the brain can be detected in around 34 per cent of patients after carotid endarterectomy (CEA) and 54 per cent after carotid angioplasty and stenting (CAS). This study compared the risk of new infarctions in the brain in patients undergoing CEA or CAS. METHODS: Consecutive patients with internal carotid artery (ICA) stenosis exceeding 70 per cent were screened for inclusion in this prospective study. Patients with indications for intervention, and eligible for both methods, were allocated randomly to CEA or CAS. Neurological examination, cognitive function tests and MRI of the brain were undertaken before and 24 h after intervention. RESULTS: Of 150 randomized patients, 73 (47 men; mean age 64·9(7·1) years) underwent CEA and 77 (58 men; 66·4(7·5) years) had CAS. New infarctions on MRI were found more frequently after CAS (49 versus 25 per cent; P = 0·002). Lesion volume was also significantly greater after CAS (P = 0·010). Multiple logistic regression analyses identified intervention in the right ICA as the only independent predictor of brain infarction (odds ratio 2·10, 95 per cent c.i. 1·03 to 4·25; P = 0·040). Stroke or transient ischaemic attack occurred in one patient after CEA and in two after CAS. No significant differences were found in cognitive test results between the groups. CONCLUSION: These data confirm a higher risk of silent infarction in the brain on MRI after CAS in comparison with CEA, but without measurable change in cognitive function. REGISTRATION NUMBER: NCT01591005 ( http://www.clinicaltrials.gov).

Endovascular treatment of acute basilar artery occlusion: time to treatment is crucial.

AIM: To evaluate the safety and efficacy of multimodal endovascular treatment (EVT) of acute basilar artery occlusion (BAO), including bridging therapy [intravenous thrombolysis (IVT) with subsequent EVT], to compare particular EVT techniques and identify predictors of clinical outcome. MATERIALS AND METHODS: This retrospective, multi-centre study comprised 72 acute ischaemic stroke patients (51 males; mean age 59.1 ± 13.3 years) with radiologically confirmed BAO. The following data were collected: baseline characteristics, risk factors, pre-event antithrombotic treatment, neurological deficit at time of treatment, localization of occlusion, time to therapy, recanalization rate, post-treatment imaging findings. Thirty- and 90-day outcomes were evaluated using the modified Rankin scale with a good clinical outcome defined as 0-3 points. RESULTS: Successful recanalization was achieved in 94.4% patients. Stepwise binary logistic regression analysis identified the presence of arterial hypertension (OR = 0.073 and OR = 0.067, respectively), National Institutes of Health Stroke Scale (NIHSS) at the time of treatment (OR = 0,829 and OR = 0.864, respectively), and time to treatment (OR = 0.556 and OR = 0.502, respectively) as significant independent predictors of 30- and 90-day clinical outcomes. CONCLUSION: Data from this multicentre study showed that multimodal EVT was an effective recanalization method in acute BAO. Bridging therapy shortens the time to treatment, which was identified as the only modifiable outcome predictor.

Predictors of good clinical outcome in acute stroke patients treated with intravenous thrombolysis.

OBJECTIVES: Intravenous thrombolysis (IVT) is considered an effective treatment for acute ischemic stroke (IS). However, not all treated patients may achieve good outcome. The aim was to evaluate whether the initial NIHSS and DWI infarct volume could be the predictors for good outcome after IVT. PATIENTS AND METHODS: The set of 125 patients with consecutive hemispheric IS (78 men; mean age 66.0 ± 12.1 years) treated with IVT within 3 h was analyzed. DWI volume was measured on admission. Good outcome was defined as a score 0-2 in modified Rankin Scale. RESULTS: Multivariate logistic regression analysis showed initial NIHSS as an independent predictor of good outcome (P = 0.001). ROC curves showed baseline NIHSS ≤13.5 points and DWI volume ≤13.7 ml as cut-offs related to good outcome. CONCLUSIONS: The initial NIHSS and DWI volume might be the predictors for good clinical outcome in acute stroke patients treated with IVT. The initial NIHSS score seems to be more accurate.

Thrombolytic treatment of ischaemic stroke occurring during a migrainous attack: a case report.

Authors report a case of young female suffering from the acute ischaemic stroke with right-sided hemiplegia, hemianopsia and hemihypoaesthesia during a migrainous attack without aura. Magnetic resonance imaging detected infarction in the left occipital lobe and occlusion of branches of the posterior cerebral artery (PCA). Combined treatment with systemic thrombolysis and sonothrombolysis was used, leading to the early PCA recanalization, and to a favourable clinical outcome after 1 month. Intravenous thrombolytic treatment administered within the therapeutic window may be useful in cerebral ischaemia associated with migraine when an arterial occlusion is documented.

Occurrence of diabetes mellitus in spontaneous intracerebral hemorrhage.

The role of diabetes mellitus (DM) in the etiopathogenesis of spontaneous intracerebral hemorrhage (SICH) is controversial. The aim was to assess the role of DM in our SICH patients. In a hospital-based cross-section study, the occurrence of DM prior to a hemorrhagic stroke was observed in 80 SICH patients (44 males, aged 36-87 years, mean 67.1 +/- 11.9 years; 36 females, aged 56-86 years, mean 71.1 +/- 8.3 years), and in a control group (CG) of 80 age- and sex-matched patients with low back pain. All patients were treated at the Departments of Neurology and Neurosurgery, University Hospital, Olomouc, Czech Republic. Two-sample t test and Pearson's homogeneity chi(2) test were applied when assessing statistical significance. DM was found in 37.5% of SICH patients versus 22.5% of CG subjects (P < 0.05). DM occurs significantly more frequently in SICH patients in the Olomouc region of the Czech Republic when compared to the general population.

Improved phytoaccumulation of cadmium by genetically modified tobacco plants (Nicotiana tabacum L.). Physiological and biochemical response of the transformants to cadmium toxicity.

The response of tobacco plants (Nicotiana tabacum L.)--non-transformed and transformed with a metallothionein gene MThis from Silene vulgaris L.--to increase cadmium supply in the nutrient solution was compared. The transgenic plants accumulated significantly more Cd both in the roots and the leaves. Visual toxicity symptoms and disturbance in water balance were correlated with Cd tissue content. Treatment with 300 microM CdCl(2) resulted in inhibition of photosynthesis and mobilization of the ascorbate-glutathione cycle. Treatment with 500 microM CdCl(2) led to irreversible damage of photosynthesis and oxidative stress. An appearance of a new peroxidase isoform and changes in the leaf polypeptide pattern were observed at the highest Cd concentration. The level of non-protein thiols gradually increased following the Cd treatment both in transgenic and non-transformed plants.

High-dose chemotherapy, fractionated total-body irradiation, and allogeneic marrow transplantation for malignant lymphoma.

Seventeen patients with malignant lymphoma, including 13 with progressive disease and four in remission following primary chemotherapy, received high-dose chemotherapy, fractionated total-body irradiation (TBI), and allogeneic marrow transplants. Eleven of the 13 (85%) patients in relapse who received transplants achieved remission, and three remain disease free 41, 21, and 17 months later; one patient in second remission who received a transplant is disease free at 11 months. Thirteen patients are dead: four because of progressive lymphoma, seven because of interstitial pneumonitis, and two because of complications of severe acute graft-v-host disease. These results are similar to those noted in marrow transplantation series for advanced acute leukemia; since transplantation during remission has decreased relapse and improved survival in leukemia, earlier transplantation may produce improved results in lymphoma patients as well. However, the effectiveness of conventional therapy regimens for most lymphomas and the high incidence of severe transplant-related complications usually limit allogeneic transplantation to lymphoma patients in situations other than consolidation of first remission. Initial partial remission, early relapse from an initial remission, and perhaps second remission are situations in which conventional therapy is often ineffective, but the adverse features of very advanced lymphoma are not present; marrow transplantation may be considered in eligible patients. Transplant recipients with more advanced disease are anticipated to have poorer survivals.

High-dose cytosine arabinoside therapy with and without anthracycline antibiotics for remission reinduction of acute nonlymphoblastic leukemia.

Seventy-eight patients with acute nonlymphoblastic leukemia in relapse were treated with high-dose cytosine arabinoside (3 g/m2 intravenously (IV) every 12 hours for 12 doses) alone, or with three days of anthracycline antibiotics (doxorubicin 20 mg/m2 or daunorubicin 30 mg/m2 IV daily) after completing the course of cytosine arabinoside. Consolidation and maintenance therapy was not given. When anthracyclines were added there was no increase in frequency or severity of nonhematologic toxicity including conjunctivitis, photophobia, dermatitis, cerebellar dysfunction, and gastrointestinal disturbance. All 78 patients achieved aplasia of the bone marrow. Five patients in each group died before bone marrow recovery. The use of anthracyclines did not prolong bone marrow recovery, with both groups demonstrating adequate granulocyte and platelet counts about four weeks after beginning treatment. Forty-one (53%) of the total 78 patients achieved a complete remission. In patients not clinically resistant to conventional-dose cytosine arabinoside, both regimens were equally effective inducing a complete remission (high-dose cytosine arabinoside alone, 12/19 [63%]; with anthracycline, 11/17 [65%], P = .270); in patients clinically resistant, the regimen including anthracycline was superior (15/27 [56%] v 3/15 [20%], P = .022). The duration of unmaintained response was similar (median, five months), but the longest remissions occurred when anthracyclines were used. Thus, high-dose cytosine arabinoside is effective in producing remissions in relapsed patients with acute nonlymphoblastic leukemia, and the addition of an anthracycline enhances this effect.

High-dose thiotepa with autologous bone marrow transplantation for metastatic malignant melanoma: results of phase I and II studies of the North American Bone Marrow Transplantation Group.

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.

Intensive 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma.

Intensive monochemotherapy with carmustine (BCNU) (either 1,050, 1,200, or 1,350 mg/m2) and cryopreserved autologous marrow transplantation was administered to 36 patients with malignant glioma: 27 with progressive disease and nine without progression (adjuvant therapy group). Twelve (44%) of the patients with progressive disease responded; two remain disease free 84 and 60 months after BCNU treatment. In the adjuvant therapy group, three patients remain progression free at 70, 48, and 27 months after BCNU therapy. Tumor progression posttransplantation occurred in 25 patients; six others died of therapy-induced complications. In addition, late neurologic deterioration of unknown cause has developed in two surviving patients. Results from this and other series using intensive BCNU monochemotherapy and autologous marrow transplantation for progressive malignant glioma indicate that prolonged progression-free survival can be produced in an occasional patient, an extremely unusual result with conventional chemotherapy. Although intensive BCNU and autologous marrow transplant regimens are toxic, these results are encouraging. The treatment of patients in an adjuvant fashion with BCNU and other active agents may produce improved results.

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer.

Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.

Cerebellar toxicity with high-dose cytosine arabinoside.

CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.

Allogeneic marrow transplantation for refractory Hodgkin's disease.

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.

Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease.

Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.