Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age,status at transplant,previous treatment and conditioning regimen. A single-centre experience in 127 patients

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.     

Autologous stem cell transplantation for Hodgkin's disease: busulfan,melphalan and thiotepa compared to a radiation-based regimen

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.     

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.     

Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine (Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P<0.0001). Five-year PFS/OS rates were 72%/87% after vorinostat/ GemBuMel, 55%/75% after GemBuMel, 45%/61% after BEAM, and 39%/57% after BuMel (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET-negative and PET-positive subgroups. Prior BV and vorinostat/GemBuMel were independent predictors of more favorable outcome, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET-positivity at ASCT correlated independently with unfavorable outcomes. In conclusion, post-HDC/ASCT outcomes of patients with HRR classic Hodgkin lymphoma have improved over the last 15 years. Pre-ASCT BV treatment and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.     

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.     

High-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT) as salvage therapy for relapsed osteosarcoma.

In this report, we describe our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in 15 children with relapsed osteosarcoma who were treated by members of the Cooperative Osteosarcoma Study Group. Eight patients received HDC after the first relapse, six patients after the second relapse and one after the sixth relapse. Thirteen patients underwent HDC and ASCT in complete remission and two patients had macroscopic tumor residues. Seven patients received HDC based on melphalan and etoposide. Four of these patients were treated with additional carboplatinum. Two patients received carboplatinum, etoposide, and thiotepa or cyclophosphamide. In six patients double HDC was performed. In all six of these, the first HDC consisted of thiotepa/ cyclophosphamide. The second regimens included melphalan/etposide (two patients), melphalan/etposide/ carboplatinum (one patient), and melphalan/busulfan (one patient). Three of the 15 patients died of toxic complications. Eight patients developed further relapses, two patients showed persistent disease, and two patients are presently in continuous complete remission. The probability of relapse-free survival was 0.20 +/- 0.12 within a median follow-up (MFU) of 8 months and the probability of overall survival was 0.29 +/- 0.12 after a MFU of 16 months. In conclusion, utilization of HDC and ASCT in this patient group did not significantly improve the treatment outcome compared to conventional relapse therapy.     

Autologous stem cell transplantation for advanced Hodgkin's disease in children. Spanish group for BMT in children (GETMON), Spain

This study evaluates the outcome of myeloablative chemo-radiotherapy and autologous stem cell transplantation (ASCT) in children with Hodgkin's disease (HD). Twenty children aged 5 to 18 years (median 10.8 years) at diagnosis, with relapsed, refractory or very poor prognosis HD, underwent ASCT in eight hospitals of our country. Status at transplant was: second complete remission (CR2): n = 12; further CR (CR >2): n = 3, partial remission (PR): n = 2, relapse: n = 2 and first CR (CR1): n = 1. Eighteen patients received chemotherapy-based conditioning regimens: cyclophosphamide, carmustine and etoposide (CBV): 11 (55%), carmustine, etoposide, cytarabine and melphalan (BEAM): 5, other: 2; and two patients were conditioned with TBI/Cy. Peripheral blood (PB) was the source of progenitor cells in 12 patients, BM in seven, and BM plus PB, in one. All patients engrafted. One patient died of sepsis and multiorgan failure at day 28 after transplantation. All four patients with measurable disease (PR or relapse) at transplantation attained complete remission. Five patients relapsed 5-34 months after transplant (median: 11 months). Eighteen children remain alive with a median survival time of 40 months. The projected 5-year overall survival and event-free survival (EFS) rates were 0.95 and 0.62. High-dose therapy with stem cell rescue can lead to durable remissions in children with advanced HD. Bone Marrow Transplantation (2000) 25, 31-34.     

Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine-melphalan conditioning for treatment of mature T-cell lymphomas

Among non-Hodgkin's lymphoma subtypes, T-cell phenotype confers a poor clinical prognosis. For more aggressive histologies, patients frequently present with advanced disease that is inherently chemoresistant. For cutaneous histologies, disease progresses less rapidly, but is debilitating and often incurable in the long term. Here we report the retrospective analysis of data from 27 patients with mature T-cell lymphoma treated with salvage allogeneic haematopoietic cell transplantation at the City of Hope, Duarte, CA, USA, using a reduced-intensity fludarabine/melphalan conditioning regimen between the years 2001 and 2008. Eleven of the twenty-seven patients had cutaneous T-cell lymphoma (CTCL). The majority of patients had advanced disease at the time of transplant (17/27 or 63%). Median follow-up was 36 months. We observed a 2-year OS of 55%, a PFS of 47% and a cumulative incidence of relapse/progression and non-relapse mortality (NRM) of 30 and 22%, respectively. For CTCL, patients had a 2-year PFS of 45% and NRM of 27% compared with patients with other histologies, who had a PFS of 62% and NRM of 19%. Overall, our results suggest that meaningful long-term survival rates and disease control can be achieved with acceptable non-relapse mortality in patients with mature T-cell lymphomas, including CTCL using reduced-intensity conditioning with melphalan and fludarabine.     

Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia

A total of 21 patients with myelofibrosis with myeloid metaplasia (MMM), with a median age of 54 years (range, 27-68 years), were prepared with a reduced-intensity conditioning (RIC) regimen. The patients received an allogeneic marrow (n = 3) or peripheral blood stem-cell (n = 18) transplant from HLA-matched related (n = 18) or unrelated (n = 2), or 1 Ag-mismatched related (n = 1), donors. RIC regimens included fludarabine/total body irradiation 200 cGy (n = 5) or 450 cGy (n = 1), fludarabine/melphalan (n = 7), thiotepa/cyclophosphamide (n = 7), and thiotepa/fludarabine (n = 1). At the time of transplantation, all of the patients were at intermediate (n = 13) or high (n = 8) risk, according to the Dupriez classification. Of the patients, 19 had grade III or IV marrow fibrosis. All of the patients achieved full engraftment but one. Posttransplantation chimerism analysis showed more than 95% donor cells in 18 patients, while 2 patients achieved complete donor chimerism after donor leukocyte infusion (DLI). Acute graft-versus-host disease (GVHD) grades II to IV was observed in 7 patients, grades III to IV in 2, and extensive chronic GVHD in 8 of 18 evaluable patients. There were 3 patients who died from acute GVHD, infection, and relapse. There are 18 patients alive 12 to 122 months (median, 31 months) after transplantation, and 17 are in remission (1 after a second transplantation). The use of RIC regimens in allogeneic stem cell transplantation results in prolonged survival in intermediate/high-risk MMM patients.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Single Centre Experience from North India

Autologous stem cell transplantation (ASCT) is considered as standard of care in patients with multiple myeloma (MM) patients aged 65 years or younger. We analyzed data of 94 patients of plasma cell dyscrasias who underwent 95 autologous transplants at our institute from October 2003 to Aug 2016. Other than 76 patients of newly diagnosed multiple myeloma, we also transplanted two patients of POEMS syndrome, two patients of plasma cell leukemia, three patients of concurrent light chain deposition disease, three patients of multifocal plasmacytomas, and eight patients of isolated light chain myeloma. One patient underwent transplant twice. The median age of patients was 53 years (range 21–65). The average interval between diagnosis and transplant was 10.51 ± 5.42 months. The predominant stage in the study cohort was ISS-III. IgG kappa was the commonest subtype of plasma cell dyscrasia (27.9%) followed by IgG lambda (16.27%). Renal involvement was seen in 25% patients at the time of transplantation. Following chemotherapy, 42% patients were in CR, 39% in VGPR, 5% had PR and 14% had progressive disease at the time of transplantation. All patients were conditioned with melphalan (dose 120–200 mg/m²) except for one who received an additional bortezomib for his second transplant. The mean time to neutrophil and platelet engraftment was 11.09 ± 1.82 and 12.69 ± 4.55 days respectively. Mucositis was noted in all patients (grade 3 in 37.5% patients). The median PFS (biochemical) was 55.8% and PFS (clinical) was 76.7% at 6.5 years. Thirteen percent of the transplanted patients succumbed to their illness of which three patients died within 30 days of transplant. Median OS was 76.7% at 6.5 years. ASCT is a feasible option for MM in India and the results are comparable.     

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m2 thiotepa and 100 mg/m2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m2, melphalan (100 mg/m2) and escalating doses of carboplatin 900-1500 mg/m2) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m2 thiotepa, 100 mg/m2 melphalan and 1350 mg/m2 carboplatin. Two consecutive patients receiving 1500 mg/m2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5x10(9)/l was 9 days (range 7-12 days) and platelet count of 20x10(9)/l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.     

Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group

OBJECTIVE: Retrospective data shows that peripheral T-cell lymphoma (PTCL) patients sensitive to conventional chemotherapy for aggressive lymphomas may respond better if this treatment is consolidated with frontline autologous stem cell transplantation (ASCT). Here, we present data from a prospective phase II trial of high-dose chemotherapy and ASCT as a frontline consolidation therapy for aggressive nodal PTCL. METHODS: This study involved 26 gallium-scan-positive patients with high-risk nodal PTCL [excluding anaplastic lymphoma kinase (ALK) positive]. Patients received three courses of MegaCHOP before they were evaluated, and those that were gallium-scan-negative at this stage then received another course of MegaCHOP and ASCT. Patients who remained gallium-scan-positive received two courses of an IFE regimen (ifosfamide 10 g/m(2), etoposide 150 mg/m(2)/12 h on days 1-3) and if they at least achieved PR, they then received the transplant. RESULTS: Complete response (CR) was achieved by 12 patients (46%) after three courses of MegaCHOP and 12 patients received IFE as a salvage therapy. After the ASCT (n = 19), 89% of patients achieved CR. In contrast, six patients (23%) did not receive the transplant because of the progression of the disease (n = 5) or lethal toxicity (n = 1). One patient in first-line CR refused ASCT. After a median follow-up of 35 months, the overall survival (OS) and progression-free survival (PFS) at 3 yr was 73% and 53%, respectively. Moreover, the OS, PFS and disease-free survival (DFS) were 84%, 56% and 63%, respectively 2 yr after transplant in patients who received ASCT consolidation (n = 19). CONCLUSIONS: Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after three courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome.     

Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation

No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5 months) was significantly better than that of patients who did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.     

Outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin lymphoma patients in a centre from Turkey

Abstract

Purpose

The aim of this study is to assess the predictors of outcome in patients with relapsed or refractory Hodgkin's lymphoma (HL) receiving autologous stem-cell transplantation (ASCT)

Materials and methods

Fifty-two consecutive patients who received ASCT at the Stem Cell Transplantation Unit of Gazi University Hospital from February 2005 through June 2011 for relapsed or refractory HL were analysed retrospectively

Results

Fifty-one patients could be evaluated after transplantation, as one of the patients died in the early post-transplantation period. Complete remission was obtained in 36 (71%), partial remission in 9 (18%), stable disease in 4 (8%), and progressive disease in 2 (3%) patients. After a median follow-up of 22 (range, 0.5–75) months, 46 (88%) patients were alive. The probability of overall survival (OS), progression free survival (PFS) and transplantation related mortality at 5 years were 87, 53, and 2%, respectively. Chemosensitive relapse had a positive impact on both OS and PFS

Conclusion

ASCT remains to be the standard treatment of relapsed or refractory HL patients. Chemosensitive relapse is the most important prognostic factor determining the outcome of the ASCT.     

Melphalan 100 mg/m2 with stem cell support as first relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation

Introduction: Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high‐dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high‐dose melphalan is recommended by many current guidelines. Yet, toxicity is an important aspect in the choice of relapse treatment, and a second ASCT in this setting could be associated with enhanced toxicity. As the goal for the treatment for relapsed myeloma should be disease control while maintaining quality of life, lower doses of melphalan might be preferable. Methods and Objectives: In this retrospective study, we account for the outcome of 66 patients with myeloma in first systemic relapse after ASCT, who were treated with intermediate‐dose melphalan, 100 mg/m², and stem cell support (MEL 100). The aim was to evaluate this treatment in relation to prior response duration after initial ASCT and with respect to response rate, toxicity and survival. Results: The overall response rate was 62%. There was limited, mostly haematological, toxicity, and no treatment–related mortality was observed. The median progression‐free survival (PFS) was 8.5 months, and the median overall survival was 24 months. Patients with time to progression of 34 months or more (n = 17; ≥75th percentile) after initial ASCT had a median PFS of 12.5 months after MEL 100. Conclusion: For patients with a long‐lasting response after ASCT, MEL 100 could be a therapeutic option with low toxicity and with efficacy comparable to newer immunomodulatory drugs.     

Transplant eligibility in elderly multiple myeloma patients: Prospective external validation of the international myeloma working group frailty score and comparison with clinical judgment and other comorbidity scores in unselected patients aged 65-75 years

Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65-75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT-CI) and IMWG frailty score were obtained at diagnosis, but the intensity of treatment was left to physician's choice. The scores and age's impact on outcome was analyzed: 85 patients were judged transplant eligible, whereas 46 patients received a less intensive treatment (median follow up 27 months). No patients classified as frail had been considered eligible to ASCT with a worse outcome compared to fit and unfit patients (median PFS (progression free survival): 7.9 vs 32.9 and 29.6 months; P < .001). PFS was superior in the ASCT group (35.6 vs 19.9 months, P .013). In the ASCT group, PFS was better in patients aged 65-69 years than in patients ≥70 (51.5 vs 27.7 months, P.004). Indeed, in unfit patients aged ≥70 the PFS of the ASCT group was comparable to NO ASCT group (18 vs 27 months, P = .33) whereas in unfit patients aged 65-69 PFS was superior in the ASCT group: 43.3 vs 18.4 months, P .01. ISS III and impaired functional status independently affected PFS in a multivariate analysis (P .011 and P .006). While CCI and HCT-CI did not predict different outcome in ASCT patients, the IMWG frailty score would be of help in identifying unfit patients aged 70-75, whose outcome with ASCT selected by clinical judgment was no better than with less intensive treatments.     

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.     

Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival

The aim of the present study was to investigate the prognostic role of pre- and/or early post-autologous stem cell transplantation (ASCT) ¹⁸F-flourodeoxyglucose (FDG) positron emission tomography (PET) in patients with relapsed/refractory Hodgkin lymphoma. Forty-three consecutive patients were enrolled in this study. FDG-PET/CT was performed following salvage chemotherapy within 6 weeks of undergoing ASCT and at the first month after ASCT. FDG-PET positivity was found in 26 patients before ASCT and in 13 patients after ASCT. The patients who had negative PET scan before or after ASCT had significantly better outcomes in terms of overall survival (OS) and progression-free survival (PFS). Pre- and post-ASCT FDG-PET positivity was found to be independently associated with PFS while post-ASCT FDG-PET was an independent factor with an impact on OS in multivariate analysis. ¹⁸F-flourodeoxyglucose positron emission tomography imaging may be useful in predicting prognosis after ASCT. Furthermore, effective treatment options including allogeneic stem cell transplantation might be considered in patients with positive FDG-PET scan after salvage chemotherapy and ASCT.     

Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease

Prospective randomized studies have determined that high dose therapy and autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed Hodgkin's disease (HD); however, the role of this approach in patients with primary refractory disease has been controversial. This report is an integrated analysis of 75 consecutive patients with biopsy-confirmed primary refractory HD, who were treated with high dose chemoradiotherapy (HDT) and ASCT at the Memorial Sloan Kettering Cancer Center. The patients underwent conventional dose cytoreductive chemotherapy followed by HDT and ASCT. At a median follow-up of 10 years for surviving patients, the event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) rates were 45%, 49% and 48% respectively. Only chemosensitivity to standard-dose second-line chemotherapy (SDSC) predicted for a better survival, thus responding patients had an EFS, PFS and OS of 60%, 62% and 66%, respectively, versus 19%, 23% and 17% for patients who had a poor response to SDSC (P < 0.001). While patients with chemosensitive disease have an excellent outcome with HDT and ASCT, novel approaches are needed to cure HD patients who fail front-line and second-line chemotherapy.     

Outcomes of high-dose chemotherapy and autologous stem cell transplant in isolated locally recurrent breast cancer: a multicenter evaluation

To determine the outcomes of women with isolated loco-regional recurrence (LRR) of breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) following conventional therapy, we conducted a retrospective review of 58 patients from five institutions treated between 1990 and 1998. Forty-five patients (78%) had > or = 2 poor prognostic factors (PPF) (defined as disease-free interval preceding LRR < or = 2 years, hormone receptor negative/refractory disease, and incomplete resection). At median follow-up of 14.2 (0.5-72) months, 36 patients (62%) developed progressive disease. Disease progression usually occurred at local (27 patients) vs distant (nine patients) sites. Median time to disease progression following ASCT was 6.1 (1.3-31.4) months. At last follow-up, 23 patients (40%) had expired (all due to disease progression), and 13 (22%) were alive with, and 22 (38%) without progressive disease. By Kaplan-Meier analysis, the estimated median PFS and OS was 20.3 and 29.2 months, respectively. In a multivariate model, complete remission at time of HDCT and estrogen-receptor positive disease were predictive of significantly longer PFS and OS. The survival of this cohort was similar to previous reports of those treated with conventional therapy alone, and to those with distant metastases treated with HDCT. Frequent progression locally, suggests that strategies to improve local disease control are needed.