Efficacy and safety of Id-protein-loaded dendritic cell vaccine in patients with multiple myeloma--phase II study results.

UNLABELLED: In a phase II clinical study, pretreated multiple myeloma patients with relapsing or stable disease received autologous anticancer vaccine containing dendritic cells loaded with Id-protein. Patients received a total of 6 vaccine doses intradermally in monthly intervals. No clinical responses were observed. During the follow-up with a median of 33.1 months (range: 11-43 months), the disease remained stable in 7/11 (64%) of patients. Immune responses measured by ELISpot were noted in 3/11 (27%) and DTH skin test for Id-protein was positive in 8/11 (73%) of patients; out of those, 1/11 (9%) and 5/11 (46%), respectively, had preexisting immune response to Id-protein before the vaccination began. Outcomes were compared to those of a control group of 13 patients. A trend to lower cumulative incidence of progression in the vaccinated group was observed at 12 months from the first vaccination (p= 0.099). More patients from the control group compared to vaccinated patients required active anticancer therapy [4/11 (36%) vs. 8/13 (62%)]. Vaccines based on dendritic cells loaded with Id-protein are safe and induce specific immune response in multiple myeloma patients. Our results suggest that the vaccination could stabilize the disease in approximately two-thirds of patients. KEYWORDS: dendritic cells, immunotherapy, anticancer vaccines, Id-protein, multiple myeloma.

[Treatment of AL-amyloidosis--results from one clinic and review of published experience with new agents (bortezomib, thalidomide and lenalidomide) in AL-amyloidosis]. / Lécba AL-amyloidózvy--výsledky jednoho pracoviste a prehled publikovanych zkuseností s novými léky (bortezomibem, thalidomidem a lenalidomidem) u AL-amyloidózy.

PATIENTS: Fifteen patients with light chain deposits in the form of AL-amyloidosis and 2 patients with light chain deposition as amorphous matter (light chain deposition disease) were treated at our clinic as of 1999. Median age at the diagnosis was 63 (34-77) years. The light chain deposition caused: nephrotic syndrome in 12 (70%) patients, renal insufficiency with reduced filtration in 4 (23%) patients, cardiomyopathy in 4 (23%) patients, hepatosplenomegaly in 2 (12%) patients, manifest coagulopathy in 2 (12%) patients, periorbital hematoma in 2 (12%) patients, visceral and somatic neuropathy in 2 (12%) patients. Treatment with high-dose dexamethasone in combination with adriamycin and vincristine (VAD) or cyclophosphamide (CAD orjust CD) was used in 11 patients. In 4 patients, therapy was completed with high-dose chemotherapy and autologous transplantation; complete haematological and organ treatment response was achieved in all 4 patients with remission lasting 113+, 87+, 50, 45+ months. Of the remaining 7 patients in whom high-dose dexamethasone therapy was not completed with high-dose chemotherapy, 3 achieved complete haematological remission (CR) and very good partial remission (VGPR), with 2 patients achieving complete organ treatment response. Organ response in the third patient cannot be assessed due to the short evaluation period. PR with no organ treatment response was achieved in other 2 patients and 2 patients died during the treatment. Therapy with prednisone and alkylating cytostatics was used in 2 patients with serious organ damage, both patients died after a short period of time due to the disease and thus treatment response cannot be evaluated. Combination of thalidomide, dexamethasone and cyclophosphamide (CTD) was used in 4 patients. Two of these patients did not complete full 2 cycles, one for unmanageable thalidomide-associated constipation, the other died. Two patients underwent a total of 5 and 6 cycles of this treatment with PR effect and plateau after the previous decline of monoclonal immunoglobulin concentrations. Treatment combination of bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) was used in three patients. In one patient (6 completed CTD cycles with the PR result) this combination led to complete haematological remission, complete remission was also achieved in the second patient and the application of 2 CVD cycles led to CR in the third (5 CTD cycles with PR result). Just one of the 3 female patients has been followed up for more than 12 months and so it is possible to evaluate organ treatment response in this patient; nephrotic syndrome ceased, meaning that organ CR has been achieved. CONCLUSION: Early diagnosis (before severe organ damage occurs) enables administration of aggressive treatment (high-dose chemotherapy and autologous transplantation) with the outlook of complete haematological and organ treatment response. New drugs thalidomide and bortezomib further expand treatment armamentarium; according to our limited experience and published information, bortezomib may be considered as very effective and well tolerated agent suitable, in combination, for patients with the diagnosis of AL-amyloidosis.

[More than 10 years of complete remission of monoclonal gammopathy of undetermined significance and cessation of light chain deposition disease-associated nephrotic syndrome following treatment with vincristine, adriamycin and high-dose dexamethasone (VAD)]. / Více nez 10 let trvající kompletní remise monoklonální gamapatie nejistého významu a vymizení nefrotického syndromu vzniklého na podkladne light chain deposition disease po lécbe vinkristinem, adriamycinem a vysokými dávkami dexametazonu (VAD).

Light chain deposits in the form of amorphous material (light chain deposition disease) damage most frequently kidneys and, less frequently, they affect other organs. The incidence of light chain deposition disease is much lower than that of AL-amyloidosis. Symmetrical swelling of both legs, swelling of the eye lids, erythrocyturia and nephrotic proteinuria were the first signs of light chain deposition disease in our patient. The disease was diagnosed from kidney biopsy performed at the stage of advanced nephrotic syndrome with reduced filtration. The bone marrow aspirate contained 0.8% of plasma cells, serum contained monoclonal immunoglobulin IgG-kappa and urine contained free kappa chains. Blood count was normal and no osteolytic changes to the skeleton were identified. The patient was, therefore, diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and was treated with 10 cycles ofchemotherapy consisting of vincristine, adriamycin and high/dose dexamethasone (VAD). Following the 10th cycle, the concentration of monoclonal IgG declined below the threshold for quantitative densitometric identification, while the more sensitive immunofixation electrophoresis remained positive. However, 2 months after the completion of chemotherapy, the immunofixation electrophoresis had become negative and thus complete haematological treatment response (remission) was achieved. Restoration of the kidney function was only gradual. Proteinuria declined below 1 g/l and no erythrocyturia was present 4 years post-treatment. Proteinuria declined to 0.19 g/I, i.e., normal values, 9 years post-treatment completion. Regular follow-ups in patients with MGUS should seek to identify not only whether MGUS is transforming into malignant disease but also whether monoclonal immunoglobulin is damaging the organism. Treatment of patients with monoclonal immunoglobulin-associated damage should be initiated early as the restoration of the affected organs function (organ treatment response) after complete haematological remission is only gradual. At present, treatment regimes with high-dose dexamethasone are recommended for patients with primary systemic AL-amyloidosis. We believe that the same approach is suitable for the treatment of light chain deposition disease in MGUS patients.

[Central diabetes insipidus in adult patients--the first sign of Langerhans cell histiocytosis and Erdheim-Chester disease. Three case studies and literature review]. / Centrální diabetes insipidus u dospelých osob--první príznak histiocytózy z Langerhansových bunek a Erdheimovy-Chesterovy choroby. Popis trí prípadu a prehled literatury.

Central diabetes insipidus with an onset in adulthood is very rare. Unlike in children, central diabetes insipidus in adults is more frequently caused by inflammatory processes and neoplastic infiltrations that do not originate from the neuronal tissue than primary neuronal tissue tumours. Rare histiocytic neoplasias (Langerhans cell histiocytosis, xanthogranulomatosis and Erdheim-Chester disease) have a specific affinity to hypothalamus and the pituitary stalk not only in paediatric patients but also when occurring in adults. We describe 3 cases of central diabetes insipidus with an onset in adulthood. Diabetes insipidus was the first sign of Langerhans cell histiocytosis in 2 patients, and it was the first sign of Erdheim-Chester disease in one patient. MR imaging showed pathological infiltration and dilated pituitary stalks in all 3 patients. PET-CT proved useful in differential diagnosis, showing further extracranial pathological changes either on the basis of significant glucose accumulation or on the basis of CT imaging. The Langerhans cell histiocytosis in the first patient has also manifested itself as an infiltration of the perianal area with intensive accumulation of fluorodeoxyglucose (FDG) - SUV 8.6 and gingival inflammation indistinguishable from parodontosis. Histology of the perianal infiltrate confirmed Langerhans cell histiocytosis. Infiltration of the pituitary stalk disappeared from the MR image after 4 cycles of 2-chlordeoxyadenosin (5 mg/m2 5 consecutive days). The PET-CT of the 2nd patient showed only borderline accumulation of FDG in the ENT area, while simultaneously performed CT imaging showed cystic restructuring of the pulmonary parenchyma and nodulations consistent with pulmonary Langerhans cell histiocytosis. Bronchoalveolar lavage identified higher number of CD1 and S100 positive elements, consistent, once again, with pulmonary LCH also affecting pituitary stalk and ear canal. The PET-CT of the third patient showed increased activity in the long bones and ilium near the sacroiliac joint. Biopsy of the focus in the ilium confirmed foam histiocyte infiltration immunochemically corresponding to Erdheim-Chester disease. Additional imaging assessments revealed the presence of further signs of the disease. Pituitary infiltrate biopsy in this patient did not elucidate the diagnosis but resulted in complete panhypopituarism. Central diabetes insipidus in adulthood might be the first sign of so far undiagnosed extracranial disease, in our case of histiocytic neoplasias, and PET-CT has an excellent potential to detect extracranial symptoms of these conditions. Therefore, the high-risk pituitary stalk infiltrate biopsy should always be preceded by comprehensive examination aimed at identification of extracranial manifestations of the pituitary gland diseases.

[Complete remission of nephrotic syndrome and improvement of renal function in a patient with light chain deposition disease following high dose chemotherapy with transplantation of autologous haematopoietic stem cells. A case study and review of literature]. / Vymizení nefrotického syndromu a zlepsení funkce ledvin u nemocné s light chain deposition disease po vysokodávkované chemoterapii s autologní transplantací kmenových krvetvorných bunek. Popis prípadu a prehled literatury.

Light chain deposition disease (LCDD) damages most frequently kidneys, and less frequently other organs. The incidence of LCDD is lower than the incidence of AL-amyloidosis. Symmetric swelling of both legs was the first sign of nephrotic syndrome with renal insufficiency in our female patient. Renal biopsy specimen revealed the diagnosis of LCDD. Bone marrow biopsy contained 40% of plasma cells. Bone survey showed no osteolytic changes. These findings confirmed the diagnosis of multiple myeloma (MM) Durie Salmon stage IB with LCDD. The patient was initially treated with 4 cycles of VAD (vinkristine, adriamycine, dexamethasone) chemotherapy with no response. Followed collection of peripheral haematopoietic stem cells and later high dose chemotherapy with reduced dose of melphalan 140 mg/sqm and autologous peripheral haematopoietic stem cells transplantation. Melphalan dose was reduced because of renal insufficiency (serum creatinine 290 micromol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 micromol/l. Worsening of renal function was most likely caused by nephrotoxicity of melphalan in nephrotic syndrome. This has been previously described in patients with AL-amyloidosis, and nephrotic syndrome who were treated with high dose melphalan. This phenomenon was entitled "post conditioning renal insufficiency". Hypoalbuminemia hypoproteinemia and reduced intravascular volume and renal damage caused by amyloid deposits as well as probably, amorphous non-amyloid deposits of monoclonal immunoglobulin are likely to have contributed to nephrotoxicity of the high dose of melphalan. However, worsening of renal insufficiency was facilitated by the mucositis-associated sepsis. Follow-up examination one month after high dose chemotherapy showed complete remission, that was confirmed by further examinations. In the course of the first year after high dose chemotherapy renal function gradually improved and nephrotic syndrome completely disappeared (complete kidney remission). Proteinuria declined to 2-3 g/24 hours and glomerular filtration slowly improved. Three years after high dose chemotherapy the patient is still in complete remission of multiple myeloma and free of nephrotic syndrome, with slightly increased creatinine (160 micromol/l) that, nevertheless, has had an improving tendency over last 3 years. The present case study illustrates accomplishment of complete haematological remission with high dose chemotherapy followed by autologous haematopoietic stem cells transplantation despite complete resistance of the disease to the standard chemotherapy VAD in a patient with MM and LCDD. We draw the reader's attention to the possibility of nephrotoxic effects of high dose melphalan (post conditioning renal insufficiency) in patients with nephrotic syndrome caused by light chain deposits as AL-amyloid or amorphous light chains deposits (LCDD)and we document the importance of plasma free light chain detection.

[Treatment of Waldenström macroglobulinaemia--the experience of one centre]. / Lécba Waldenströmovy makroglobulinemie-- zkusenosti jednoho pracoviste.

Waldenström macroglobulinaemia (WM) is a disease the incidence of which is approximately 10 times lower than that of multiple myeloma. The incidence of WM is reported to be respectively 0.34 per 100,000 men and 0.7 per 100,000 women. It is one of the less aggressive lymphoproliferative diseases in which therapy is indicated only when the disease symptoms start to manifest. We present a retrospective analysis of patients with the symptomatic form of WM who were treated with chemotherapy in our centre over the last 9 years, i.e. 19 WM patients (of which 7 women and 12 men). The median age upon diagnosis of the symptomatic form of WM and start of treatment was 59 (51-78) years. The median follow up for all patients was 31 (7-121) months. The most frequent indication for WM treatment was anaemia in 57% (11/19), thrombocytopaenia in 21% (4/19), plasma hyperviscosity in 42% (8/19), symptomatic lymphadenopathy in 15% (3/19), and pathologic osteolysis in 15% (3/19) ofcases, respectively. Decrease in immunoglobulin concentration under the lower physiological limit is not referred to as a characteristic sign of WM, yet it was recorded in 7 out of 19 patients in our patient group and continued after chemotherapy, with the affected patients suffering from infections in remission more often than those with physiological values of immunoglobulins. 36% (7/19) patients were treated with R-FC (rituximab + fludarabine + cyclophosphamide) therapy, 15% (3/19) with FC therapy, 15% (3/19) with R-CHOP concluded by high-dose chemotherapy with autologous transplantation in 1 case, and 5% (1/19) with CHOP therapy. VAD (vancristine, ariamycine and dexamethasone) therapy was used in 10% (2/19) of patients and 10% (2/19) of patients were treated with oral chlorambucil. The first line of treatment achieved complete remission (CR) in 15% cases (3/15). Two patients who achieved CR were treated with R-FC, and one patient with VAD. Partial remission (PR) was achieved by 63% of patients (12/19). Minor response (MR) was achieved by 10% (2/19), and stable disease (SD) was recorded in 10% of patients (2/19) after initial treatment. The first relaps of the disease was recorded in 5 patients (2 of whom had PR and 3 MR) who achieved remission after additional lines of therapy. Thirteen patients are in the first PR. With a follow up median of 31 months (7-121), only 2 patients died from other than the underlying disease. Additional malignant disease was diagnosed in 3 patients: 1 colon carcinoma, 1 acute myeloid leukaemia (AML) and 1 myelodysplastic syndrome (MDS). All three received fludarabine and cyclophopsphamide as initial therapy. Of the three patients only the patient with MDS has survived and is now without any evidence of the presence of WM, i.e. in complete remission at 41 months after the start of therapy. High-dose chemotherapy with autologous transplantation was used in 2 cases, once as part of initial therapy and once as part of the therapy for the first relaps resistant to R-CHOP chemotherapy. It is not possible to determine the median of the first remission or the median of total survival due to the short follow up interval.

[Fever of unknown origin--etiology and diagnostic algorithm]. / Teplota nejasné etiologie: príciny a diagnostický postup.

Fever of unknown origin is a frequent and significant diagnostic problem often faced by physicians. The first part of the text is dedicated to its definition and wide-ranging aetiology. On the one hand, fever may be a banal and benign condition, on the other, it can be the symptom of a life threatening disease. The second part presents our suggestions for diagnostic approach to fever of unknown origin. We believe this text may become a useful tool for this extremely complex and interesting differential diagnostic. In view of extension and complexity of the topic, the text of this part is presented in full.

Simple variables predict survival after autologous transplantation: a single centre experience in 181 multiple myeloma patients.

Autologous stem cell transplantation (ASCT) has an important role in the treatment of multiple myeloma (MM) patients. The aim of our study was to analyse retrospectively the impact of selected simple parameters on the survival of patients with MM after ASCT, including age, type of M-protein, stage of MM, treatment response, and presence of renal impairment. A total of 181 MM patients were transplanted in our centre between 1995 and 2004. The median follow-up from transplant was 59 months. Following ASCT, 29% of patients were in complete remission (CR) and 62% in partial remission (PR); 35% of patients had very good partial response (VGPR). Median time to progression (TTP) and overall survival (OS) from start of therapy were 33.0 and 78.3 months, respectively. Significant prognostic parameters for poor survival after ASCT were: age at transplant > 60 years (P < 0.001), TTP < 20 months (P < 0.001), IgA type of monoclonal immunoglobulin (P = 0.045), renal impairment with serum creatinine > 177 micromol/l (> 2 mg/dl; P = 0.004), clinical stage III according to ISS (P = 0.002) and no achievement of CR and/or VGPR after ASCT (P < 0.001). The stage of the disease before ASCT did not significantly affect OS after ASCT.

Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients.

Autologous stem cell transplantation (ASCT) has an established role in the treatment of symptomatic multiple myeloma (MM). Our aim was to analyse the impact of selected prognostic parameters on the survival of patients with MM after ASCT. The new International Staging System (ISS) was also evaluated. A total of 133 MM patients were transplanted in our centre between 1995 and 2002. Following ASCT, 35% of patients were in complete remission (CR) and 60% were in partial remission (PR). The median progression-free (PFS) and overall (OS) survival from transplantation were 29.5 and 68.8 months, respectively. Transplant-related mortality (TRM) was 3%. On multivariate analysis, factors associated with significantly shorter OS were lack of CR after transplant (P = 0.002, hazard ratio (HR): 3.1), stage 3 according to ISS (P = 0.001, HR: 3.0) and age at transplant over 60 years (P = 0.035, HR: 2.0). The status of disease before ASCT did not significantly affect PFS and OS after transplantation. We conclude that ASCT is a safe and effective procedure in MM patients, associated with low TRM. The survival after ASCT was dependent on response after ASCT, stage according to ISS and age.

Second autologous transplantation for multiple myeloma patients relapsing after the first autograft -- a pilot study for the evaluation of experimental maintenance therapies. Report of the prospective non-randomized pilot study of the Czech Myeloma Group.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (AT) is accepted as first-line therapy for patients with multiple myeloma (MM), with very good tolerance and low mortality (2-3%). STUDY DESIGN: We tested repeated transplantation with different experimental maintenance therapies in patients with MM relapsing/progressing after first AT. Results were compared using intra-individual analyses, therefore inter-individual differences are excluded (T2 model). PATIENTS AND METHODS: Between January 1997 and January 2003, 32 patients with relapsing/progressing MM after first AT were included in the pilot study, median follow-up was 75.2 months. They received the following experimental therapies: IL-2-activated PBSC (10 pts), pamidronate (4 pts), thalidomide (15 pts), consolidation chemotherapy CED (3 pts). RESULTS: Sensitivity to C-VAD reinduction chemotherapy (4 cycles) was 50%, response to the second AT compared to the first was better in 7, the same in 16 and worse in 9 patients. Toxicity of the first and second transplantation was similar and usually did not exceed grade II (SWOG). Transplant-related mortality was 3% (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7 have achieved prolongation of EFS II versus EFS I. In the whole group median EFS I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS) was 79.1 months; 20/32 patients were alive at the time of analysis. CONCLUSIONS: Repeated AT is a feasible and successful strategy in treatment of relapsing MM; response to second AT and toxicity were acceptable and similar to the first AT in our assessment.

[High-dosage chemotherapy with support of autologous haematopoietic cells in the treatment of multiple myeloma--review of contemporary possibilities]. / Vysokodávkovaná chemoterapie s podporou autologních hemopoetických bunek v terapii mnohocetného myelomu--prehled soucasných mozností.

High-dosage chemotherapy with autologous transplantation of haematopietic stem cells prolonged the survival of patients with multiple myeloma as compared with results of standard chemotherapy, on average by 1.5 years. Nowadays this method is the standard treatment for suitable patients. Findings assembled recently are discussed by the authors.

[Haematopoietic stem cell mobilization in patients with multiple myeloma--comparison of 3 variations of the stimulating regime]. / Mobilizace kmenových krvetvorných bunek u pacientu s mnohocetným myelomem--srovnání trí variant stimulacních rezimu.

In the literature various regimes are described for successful collection of haematopoietic stem cells in patients with multiple myeloma. Most frequently cyclophosphamide is used, 5 g/m2 combined with different doses of haematopoietic growth factors. In our group the yields and tolerance of three stimulating regimes are compared: 1. cyclophosphamide 5 g/m2 and filgrastim (G-CSF) 5 micrograms/kg 2. cyclophosphamide 5 mg/m2 and filgrastim 10 micrograms/kg 3. cyclophosphamide 5 g/m2 and figrastim 5 micrograms/kg along with erythropoitin 50 IU/kg. Cyclophsphamide is administered always on the first day and the haematopoietic growth factors then from the third day till the end of collection of haematopoitic cells. In patients with multiple myeloma where only four cycles of VAD chemotherapy preceded and where radiotherapy of the axial skeleton was not used, optimal collection of haematopoietic stem cells was achieved after administration of cyclohosphamide 5 g/m2 with subsequent administration of 5 micrograms/kg G-CSF. By increasing the dose of G-CSF to 10 micrograms/kg or adding 50 IU/kg erthropoietin did not lead to a significant improvement of the tolerance and yield of this procedure.

[Detection of myeloma cells in peripheral blood using multi-parameter flow cytometry: monitoring residual disease]. / Detekce myelomových bunek v periferní krvi vícerozmernou prutokovou cytometrií: monitorování zbytkové nemoci.

BACKGROUND: The aim of this study was to evaluate significance of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells counts in peripheral blood of patients with multiple myeloma for monitoring of the minimal residual disease. METHODS AND RESULTS: A triple-color flow cytometric analysis was used for this purpose. Peripheral blood of 29 patients with multiple myeloma who underwent high dose chemotherapy and autologous stem cells transplantation was repeatedly analysed. Counts of myeloma cells in peripheral blood were compared to serum monoclonal immunoglobulin concentration, serum calcium level, serum C-reactive protein, serum beta 2 microglobulin, and number of myeloma cells in bone marrow (morphology). From 29 patients in this study, 5 patients have relapsed. Patients in relapse had significantly higher counts of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells in peripheral blood than patients in remission (geometrical average: 12.41; 6.20; 14.45 cells/microliter versus 4.08; 2.87; 2.58 cells/microliter). The number of these cells correlated well with serum monoclonal immunoglobulin level and counts of myeloma cells in bone marrow. CONCLUSION: The authors conclude that the longitudinal multi-color flow cytometric analysis of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells in peripheral blood of patients with multiple myeloma is a useful method for evaluation of the disease activity. Significance of peripheral myeloma cells count for prediction of the relapse of the multiple myeloma remains to be evaluated.

[The POEMS syndrome: a case report]. / "POEMS" syndrom: popis prípadu.

The POEMS syndrome is a synopsis of different symptoms such as polyneuropathy, organomegaly, endocrine disturbances, M-protein and skin changes. POEMS syndrome has a complete and incomplete form. The leading symptoms are neuropathy and the monoclonal gammopathy. The authors report about a 55 year old lady who fell ill with this disease.

Current role of immunotherapy in multiple myeloma.

Myeloablative chemotherapy improved the results of multiple myeloma treatment but the disease remains incurable. Residual disease eradication is one of the main clues for further improvement of the prognosis of myeloma patients. Interferon alpha maintenance therapy has controversial results. New methods, such as consolidation therapy, antibodies, gene therapy, interleukins, immunotoxins, dendritic cells, vaccines and induction of graft-versus-tumor effect, are tested in the phase I/II clinical trials. This article briefly reviews the new treatment modalities of immunotherapy. Progress in adoptive cellular immunotherapy and progress in induction of graft versus myeloma effect are very promising. We are still not able to transfer very good preclinical results of immunotherapy into clinical results in vivo measured by event free and long-term survivals. Combination of myeloablative therapy followed a new type of immunotherapy focusing on residual disease eradication evaluated in the setting of sensitive disease may be optimal. Such approach could improve the current controversial status of immunotherapy in MM.