Search

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of

To compare bone marrow biopsy (BMB) and PET/CT in detecting bone marrow involvement in Hodgkin's lymphoma MATERIAL AND METHODS: Retrospective analysis of 65 patients with both tests in the initial staging or in relapse with special attention to the PET/CT uptake pattern.In 3 patients (4.6%), the BMB showed bone marrow involvement with the PET/CT being positive in them all: 2 with diffuse+multifocal pattern and one diffuse only. In 11 additional patients (total 14/65, 21%), bone marrow involvement was diagnosed by PET/CT because bone marrow uptake was above hepatic one. The pattern was focal only in 2 cases, multifocal in 5, diffuse in 3 and diffuse+multifocal in one. In these last 4 cases the BMB showed an unspecific myelopathy.PET/CT detects all cases with BMB affected and many that escape to biopsy, however when the uptake pattern is diffuse it could be by involvement or reactive hyperplasia and in those cases the BMB should be done.

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Espafiol de Linfomas y Trasplantes de Medula Osea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease = 2 or PR >= 2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL. (C) 2017 American Society for Blood and Marrow Transplantation.

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

A histomorphometric analysis of the length of reticulin fibres per area of haemopoietic bone marrow was performed on 59 trephine iliac crest biopsies. The values obtained were found to correlate with the degree of fibrosis as determined by a simple optical method based on the degree of microscopic magnification required for recognition of the presence of reticulin fibres. The mean length of fibre (microns/10,000 micron2) for the three degrees of fibrosis defined by the optical method were: 241.8 +/- 16.6 for grade I, 713 +/- 85.6 for grade II, and 1827.9 +/- 230.4 for grade III (P < 0.001). In a series of 67 biopsies, the overall interobserver agreement of the optical method was found to be good (Spearman's r = 0.99; P < 0.001) and there was good individual agreement for each of the three degrees of fibrosis (improved kappa test). There was a small amount of overlap between the extreme values of adjacent optical degrees. These results suggest that the optical method described here can be recommended as a practical technique for the routine evaluation of myelofibrosis.

Objective: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. Design: Cross-sectional prospective study. Setting: Detoxication unit and internal medicine unit of a university hospital. Patients: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. Results: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 ± 89 kcal/day in females and 1265 ± 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. Conclusions: Many drug addicts suffer from calorie and protein malnutrition. This malnutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (>= 25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease.

27 páginas, 3 figuras, 2 tablas.-- et al., Background The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m2 and melphalan 200 mg/m2 as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study. Design and Methods The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m2; because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m2. Results Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m2 resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m2 group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m2 (58%; P=0.01). Conclusions Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m2 but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients., This research was supported by grant PI051284 from the Fondo de Investigación Sanitaria (FIS), Instituto Carlos III, Ministerio de Sanidad, by the Cooperative Research Thematic Network (G03/136 and RD06/0020/0006), and by the Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (PI060339 and 02/0905).

Purpose Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM. Patients and Methods We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation. Results Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10−5) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival. Conclusion Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.

Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients.Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy.The mobilization regimens consisted of standard or high-dose granulocyte colony-stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in 206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388 patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%). Multivariate analysis indicated that advanced age (p0.0001) and longer interval between diagnosis and mobilization (p=0.012) were the two variables associated with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were not observed between the mobilization regimens. Of the 789 patients included in the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9) neutrophils/L could be recovered after 11 days (median time; range, 5-71 days) and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6-69 days).A short-course of therapy with alkylating agents according to the GEM-2000 protocol was associated with an appropriate CD34+ cell collection, and allowed the planned ASCT to be performed in the majority of MM patients.

Bone marrow biopsy (BMB) is generally performed either on the anterior superior iliac spine (ASIS) or the posterior superior iliac spine (PSIS), the choice between these two sites depending largely upon practice at individual centres. No previous study has attempted to ascertain which of these two sites is preferable for needle BMB. We studied 72 biopsies, of which 36 were of the PSIS and 36 of the ASIS, measuring the length of the cylinder and the area of the histologic section. We asked those patients who had undergone BMB at both sites which had been the less painful. The cylinders obtained from the PSIS were found to have a significantly greater length and area than those obtained from the ASIS (P < 0.00001). Of the 13 patients who underwent BMB at both sites, 11 reported the PSIS biopsy to have been distinctly less painful (P = 0.012). We conclude that needle BMB of the PSIS provides samples of greater length and area, and is less painful, than that of the ASIS.