Background and objectives: Although alkylating agents are clearly beneficial in multiple myeloma ... more Background and objectives: 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. Design and methods: 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. Results: 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 (p<0.0001) 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). Interpretation and conclusions: 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.
Authors study growth patterns of granulocytic-macrophagic progenitors in umbilical cord blood of ... more Authors study growth patterns of granulocytic-macrophagic progenitors in umbilical cord blood of 21 full-term newborns, using collagen gel culture method. Predominantly they obtain pure macrophagic colonies or mixed granulocytic colonies. After 7 days of incubation mean and SD of clusters in 103.22 +/- 75.88, and mean and SD of colonies is 34.26 +/- 23.1. After 14 days clusters falls down until 47.2 +/- 30.48, but colonies goes up to 74.2 +/- 32.78. Lineal regression analysis shows a correlation coefficient of 0.809 between 7 days and 14 days colonies. These results demonstrate the different behaviour between myelopoietic progenitor from umbilical cord blood and same progenitor from adult blood and are probably related to different nature of both progenitors.
The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult ... more The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).
Summary. We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and... more Summary. We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1–3; cyclophosphamide 200 mg/m2 IV, d 1–3; and mitoxantrone 6 mg/m2 IV, d 1, at 4‐week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. ‘In vitro’ sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1–6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(–)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. ‘In vitro’ sensitivity also correlated with CR achievement (P = 0·04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment‐related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(–), in patients with previously treated CLL.
We have analysed the influence of age on survival after a tandem hematopoietic stem cell transpla... more We have analysed the influence of age on survival after a tandem hematopoietic stem cell transplantation prospective protocol (GEM-2000) in patients diagnosed of multiple myeloma (MM). From 870 patients with symptomatic MM aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 70 years and prospectively included in the GEM-2000 protocol, we have analysed the outcome of a group of 637 patients [351 males, median age of 59 (range, 32 – 70) years] and treated with at least one autologous stem cell transplantation (ASCT). Sixteen patients (2.5%) were between 31 and 40 years of age (group A), 96 patients (15%) between 41 and 50 years (group B), 244 patients (38%) between 51 and 60 years (group C) and the remaining 281 patients (44.5%), between 61 and 70 years (group D). In 325 patients the M component at diagnosis was an IgG (51%). Fifty three patients (8%) had stage I at diagnosis, 232 patients (37%) stage II and 352 patients (55%), stage III. One hundred and one patients (16%) presented with renal insufficiency at diagnosis. Significantly lower levels of serum albumin at diagnosis were observed in the older group of patients (3.88 g/L vs 4.46 g/L, p = 0.05). Most of the patients (612, 96%) were initially treated with the alternating protocol VBCMP/VBAD. The response rate to the first line therapy was of 84% (n = 533), without differences between group D and the rest of the groups. The BUMEL protocol (busulfan 10 mg/kg po plus melphalan 140 mg/m2 iv) and MEL200 (melphalan 200 mg/m2 iv) were the two conditioning regimens used for the first intensive procedure. Although the proportion of older patients (group D) who received MEL200 was higher than in the younger groups of patients (groups A – C) (35% vs 44%), these differences did not reach a statistical significance. At three months after the first ASCT, 30% of the patients had reached a complete remission with negative immunofixation (CR IF-); this percentage was significantly superior in the younger group of patients (groups A – C) with respect to group D (32% vs 27%, p = 0.02). Transplant related mortality (TRM) was also significantly superior in group D (8% vs 3%, p = 0.01). At the time of follow-up, 124 patients (19%) have received a second transplantation; a second intensive procedure was more frequently performed in the younger group with respect to group D (25% vs 12%, p = 0.0001). This second transplant was an ASCT in 73% of the patients (65% in groups A – C vs 94% in group D, p = 0.04). With a median follow-up of 24 months, 508 patients are alive. Actuarial 2-year overall survival (OS) and event free survival (EFS) for the whole population of patients are 75%±2% and 57%±2%, respectively, with statistically significant differences between groups A - C and group D (77%±3% vs 72%±3%, p = 0.05 and 62%±3% vs 52%±4%, p = 0.02, respectively). The overall benefit of the intensification procedure seems to be less in the older group of MM patients (61 – 70 years) included in the GEM-2000 protocol. These results could be related to the achievement of a significant lower rate of CR IF- after the first ASCT and a higher TRM in this older population of patients.
Abstract 658 The HDR-allo trial was a prospective phase II study evaluating the feasibility and s... more Abstract 658 The HDR-allo trial was a prospective phase II study evaluating the feasibility and safety of RIC-allo in relapsed or refractory HL. Patients (pts) were eligible if they had achieved complete remission (CR), partial remission (PR), or stable disease after salvage chemotherapy. The conditioning regimen consisted of fludarabine (150 mg/m2) and melphalan (140 mg/m2); graft-versus-host disease (GVHD) prophylaxis combined cyclosporine A and short-course methotrexate. From March 2000 to September 2007, 88 pts were included; 10 pts progressed after salvage therapy, 78 pts proceeded to RIC-allo. There were 49 males, the median age was 32 (range: 18-55) years at the time of RIC-allo. 70 pts had failed &gt; 2 lines of therapy, 68 pts had received radiotherapy, and 67 pts (86%) had failed a prior autograft (ASCT). Median time from diagnosis to RIC-allo was 46 (range: 9-300) months, median time to progression from ASCT was 8 (range: 2-144) months. 52 pts were allografted with sensitive disease (CR or PR), the remaining 28 pts were grafted with resistant disease. A matched sibling donor was available in 55 pts (70%), a matched unrelated donor (MUD) was used in 23 pts; the MUD pts received ATG (90 mg/kg) as additional GVHD prophylaxis. Stem cells were derived from peripheral blood in 75 pts. Cumulative incidence of non-relapse mortality (NRM) was 15% and 19% at 1 and 3 years, respectively, it was adversely influenced by poor performance status (ECOG ≤ 2) [relative risk 3.9, 95% confidence interval (CI) 1.8–7.3, p = 0.05] and refractory disease at the time of transplant [relative risk 2.6, 95%CI 1.5–4.5, p = 0.01]. Cumulative incidence of acute GVHD was 32% at 100 days, cumulative incidence of chronic GVHD (cGVHD) was 40% and 44% at 1 and 2 years, respectively. The development of cGVHD was significantly associated with a reduced relapse rate (36% vs 60%, p = 0.05). With a median (range) time to relapse of 6 (3–35) months, relapse rate was 37% and 59% at 1 and 3 years, respectively. Having failed &gt; 3 lines of therapy and refractory disease at the time of transplant were independent adverse prognostic factors (p = 0.03 and p = 0.01, respectively). With a median follow up of 38 (range: 12-69) months, PFS was 50% and 25% at 1 and 3 years, respectively. It was adversely influenced by refractory disease at the time of RIC-allo (64% for sensitive vs. 25% for refractory pts at 1 year, p &lt; 0.001). OS was 71% and 43% at 1 and 3 years, respectively. It also was significantly lower in pts with refractory disease (80% in sensitive vs. 56% in refractory pts at 1 year). 25 pts received donor lymphocyte infusions (DLI). 14 pts received DLI alone; in 9 pts a combination with chemotherapy was given. Response rate (CR/PR) was 40% for patients receiving DLI alone and 53% for those receiving the combination. No differences in any outcome parameter were observed between sibling and MUD transplants. In conclusion, RIC-allo is a feasible and relatively safe procedure also in heavily pretreated HL patients. Results are more promising in pts with chemosensitive disease at transplantation (64% PFS at 1 year). No difference was observed between patients allografted from HLA-identical siblings or MUD. The lower relapse rate in pts developing cGVHD, the response rate of 43% after DLI, and the existence of long-term disease free survivors are all indicators of a clinically relevant graft-versus-HL effect. The high relapse rate remains the major clinical problem. More intense (intermediate) conditioning and RIC-allo earlier in the course of disease will be evaluated in further studies. Disclosures: No relevant conflicts of interest to declare.
Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Mult... more Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Multiple in Spain. The heterogeneity and complexity of this pathology, and the several sociodemographic factors, justify the interest of this type of studies. On the other hand, this disease needs a high assignement of welfare and therapeutic resources, and besides new strategies have arisen for its treatment. The Spanish Leukaemia and Lymphoma Foundation (FLL)has analyzed the actual situation of Myeloma Multiple in Spain, compiling several epidemiologic and welfare parameters about the disease in a Multiple Myeloma “White Book” for Spain. Patients and Methods The period of analysis was 10 years, from 1.991 to 2.001. The information was compiled from a Hospital Based Survey about MM and the following official sources: International Agency for Research on Cancer (IARC): “Cancer incidence in Five continents” and “Incidence and Mortaliity for Cancer In Spain, Patterns and Tendences” Data Base o...
3951 Aim: The aims of this study were on one hand, to evaluate the significance of achieving mole... more 3951 Aim: The aims of this study were on one hand, to evaluate the significance of achieving molecular response (MR) by fluorescent-PCR (F-PCR) of Ig genes in a prospective way, particularly in patients with singular…
One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS ... more One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show benefit from a second transplant. The aim of our study was to investigate the efficacy in terms of response improvement and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first high-dose procedure. Patients diagnosed with MM from Oct 1999 to Dec 2004 younger than 70 years received 6 courses of VBMCP/VBAD and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (second auto with CVB - cyclophosphamide, etoposide and BCNU - or MEL-200 intensification or an allo-RIC with Fludarabine/MEL-140 conditioning, if sibling donor available). Eighty-eight patients received a seco...
We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC... more We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology. Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional pr...
Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia... more Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia in patients over 60 years old. Results of the CETLAM AML-99 protocol Intensive induction and consolidationtherapy with agents such as idarubicin1,2and high-dose cytarabine3-6 and hema-topoietic stem cell transplantation7 are the mainstay in the treatment of acute myeloid leukemia (AML). However, while the inci-dence of AML increases with age, these treatments provide greater benefit to younger rather than to older patients. More than one half of the patients with AML are older than 60 years8 and, therefore, most are not candidates for intensive therapies because of co-morbid conditions or
For establishing the true effect of different response categories in patients with multiple myelo... more For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10−5); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are ali...
Background and objectives: Although alkylating agents are clearly beneficial in multiple myeloma ... more Background and objectives: 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. Design and methods: 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. Results: 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 (p<0.0001) 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). Interpretation and conclusions: 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.
Authors study growth patterns of granulocytic-macrophagic progenitors in umbilical cord blood of ... more Authors study growth patterns of granulocytic-macrophagic progenitors in umbilical cord blood of 21 full-term newborns, using collagen gel culture method. Predominantly they obtain pure macrophagic colonies or mixed granulocytic colonies. After 7 days of incubation mean and SD of clusters in 103.22 +/- 75.88, and mean and SD of colonies is 34.26 +/- 23.1. After 14 days clusters falls down until 47.2 +/- 30.48, but colonies goes up to 74.2 +/- 32.78. Lineal regression analysis shows a correlation coefficient of 0.809 between 7 days and 14 days colonies. These results demonstrate the different behaviour between myelopoietic progenitor from umbilical cord blood and same progenitor from adult blood and are probably related to different nature of both progenitors.
The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult ... more The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).
Summary. We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and... more Summary. We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1–3; cyclophosphamide 200 mg/m2 IV, d 1–3; and mitoxantrone 6 mg/m2 IV, d 1, at 4‐week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. ‘In vitro’ sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1–6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(–)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. ‘In vitro’ sensitivity also correlated with CR achievement (P = 0·04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment‐related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(–), in patients with previously treated CLL.
We have analysed the influence of age on survival after a tandem hematopoietic stem cell transpla... more We have analysed the influence of age on survival after a tandem hematopoietic stem cell transplantation prospective protocol (GEM-2000) in patients diagnosed of multiple myeloma (MM). From 870 patients with symptomatic MM aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 70 years and prospectively included in the GEM-2000 protocol, we have analysed the outcome of a group of 637 patients [351 males, median age of 59 (range, 32 – 70) years] and treated with at least one autologous stem cell transplantation (ASCT). Sixteen patients (2.5%) were between 31 and 40 years of age (group A), 96 patients (15%) between 41 and 50 years (group B), 244 patients (38%) between 51 and 60 years (group C) and the remaining 281 patients (44.5%), between 61 and 70 years (group D). In 325 patients the M component at diagnosis was an IgG (51%). Fifty three patients (8%) had stage I at diagnosis, 232 patients (37%) stage II and 352 patients (55%), stage III. One hundred and one patients (16%) presented with renal insufficiency at diagnosis. Significantly lower levels of serum albumin at diagnosis were observed in the older group of patients (3.88 g/L vs 4.46 g/L, p = 0.05). Most of the patients (612, 96%) were initially treated with the alternating protocol VBCMP/VBAD. The response rate to the first line therapy was of 84% (n = 533), without differences between group D and the rest of the groups. The BUMEL protocol (busulfan 10 mg/kg po plus melphalan 140 mg/m2 iv) and MEL200 (melphalan 200 mg/m2 iv) were the two conditioning regimens used for the first intensive procedure. Although the proportion of older patients (group D) who received MEL200 was higher than in the younger groups of patients (groups A – C) (35% vs 44%), these differences did not reach a statistical significance. At three months after the first ASCT, 30% of the patients had reached a complete remission with negative immunofixation (CR IF-); this percentage was significantly superior in the younger group of patients (groups A – C) with respect to group D (32% vs 27%, p = 0.02). Transplant related mortality (TRM) was also significantly superior in group D (8% vs 3%, p = 0.01). At the time of follow-up, 124 patients (19%) have received a second transplantation; a second intensive procedure was more frequently performed in the younger group with respect to group D (25% vs 12%, p = 0.0001). This second transplant was an ASCT in 73% of the patients (65% in groups A – C vs 94% in group D, p = 0.04). With a median follow-up of 24 months, 508 patients are alive. Actuarial 2-year overall survival (OS) and event free survival (EFS) for the whole population of patients are 75%±2% and 57%±2%, respectively, with statistically significant differences between groups A - C and group D (77%±3% vs 72%±3%, p = 0.05 and 62%±3% vs 52%±4%, p = 0.02, respectively). The overall benefit of the intensification procedure seems to be less in the older group of MM patients (61 – 70 years) included in the GEM-2000 protocol. These results could be related to the achievement of a significant lower rate of CR IF- after the first ASCT and a higher TRM in this older population of patients.
Abstract 658 The HDR-allo trial was a prospective phase II study evaluating the feasibility and s... more Abstract 658 The HDR-allo trial was a prospective phase II study evaluating the feasibility and safety of RIC-allo in relapsed or refractory HL. Patients (pts) were eligible if they had achieved complete remission (CR), partial remission (PR), or stable disease after salvage chemotherapy. The conditioning regimen consisted of fludarabine (150 mg/m2) and melphalan (140 mg/m2); graft-versus-host disease (GVHD) prophylaxis combined cyclosporine A and short-course methotrexate. From March 2000 to September 2007, 88 pts were included; 10 pts progressed after salvage therapy, 78 pts proceeded to RIC-allo. There were 49 males, the median age was 32 (range: 18-55) years at the time of RIC-allo. 70 pts had failed &gt; 2 lines of therapy, 68 pts had received radiotherapy, and 67 pts (86%) had failed a prior autograft (ASCT). Median time from diagnosis to RIC-allo was 46 (range: 9-300) months, median time to progression from ASCT was 8 (range: 2-144) months. 52 pts were allografted with sensitive disease (CR or PR), the remaining 28 pts were grafted with resistant disease. A matched sibling donor was available in 55 pts (70%), a matched unrelated donor (MUD) was used in 23 pts; the MUD pts received ATG (90 mg/kg) as additional GVHD prophylaxis. Stem cells were derived from peripheral blood in 75 pts. Cumulative incidence of non-relapse mortality (NRM) was 15% and 19% at 1 and 3 years, respectively, it was adversely influenced by poor performance status (ECOG ≤ 2) [relative risk 3.9, 95% confidence interval (CI) 1.8–7.3, p = 0.05] and refractory disease at the time of transplant [relative risk 2.6, 95%CI 1.5–4.5, p = 0.01]. Cumulative incidence of acute GVHD was 32% at 100 days, cumulative incidence of chronic GVHD (cGVHD) was 40% and 44% at 1 and 2 years, respectively. The development of cGVHD was significantly associated with a reduced relapse rate (36% vs 60%, p = 0.05). With a median (range) time to relapse of 6 (3–35) months, relapse rate was 37% and 59% at 1 and 3 years, respectively. Having failed &gt; 3 lines of therapy and refractory disease at the time of transplant were independent adverse prognostic factors (p = 0.03 and p = 0.01, respectively). With a median follow up of 38 (range: 12-69) months, PFS was 50% and 25% at 1 and 3 years, respectively. It was adversely influenced by refractory disease at the time of RIC-allo (64% for sensitive vs. 25% for refractory pts at 1 year, p &lt; 0.001). OS was 71% and 43% at 1 and 3 years, respectively. It also was significantly lower in pts with refractory disease (80% in sensitive vs. 56% in refractory pts at 1 year). 25 pts received donor lymphocyte infusions (DLI). 14 pts received DLI alone; in 9 pts a combination with chemotherapy was given. Response rate (CR/PR) was 40% for patients receiving DLI alone and 53% for those receiving the combination. No differences in any outcome parameter were observed between sibling and MUD transplants. In conclusion, RIC-allo is a feasible and relatively safe procedure also in heavily pretreated HL patients. Results are more promising in pts with chemosensitive disease at transplantation (64% PFS at 1 year). No difference was observed between patients allografted from HLA-identical siblings or MUD. The lower relapse rate in pts developing cGVHD, the response rate of 43% after DLI, and the existence of long-term disease free survivors are all indicators of a clinically relevant graft-versus-HL effect. The high relapse rate remains the major clinical problem. More intense (intermediate) conditioning and RIC-allo earlier in the course of disease will be evaluated in further studies. Disclosures: No relevant conflicts of interest to declare.
Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Mult... more Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Multiple in Spain. The heterogeneity and complexity of this pathology, and the several sociodemographic factors, justify the interest of this type of studies. On the other hand, this disease needs a high assignement of welfare and therapeutic resources, and besides new strategies have arisen for its treatment. The Spanish Leukaemia and Lymphoma Foundation (FLL)has analyzed the actual situation of Myeloma Multiple in Spain, compiling several epidemiologic and welfare parameters about the disease in a Multiple Myeloma “White Book” for Spain. Patients and Methods The period of analysis was 10 years, from 1.991 to 2.001. The information was compiled from a Hospital Based Survey about MM and the following official sources: International Agency for Research on Cancer (IARC): “Cancer incidence in Five continents” and “Incidence and Mortaliity for Cancer In Spain, Patterns and Tendences” Data Base o...
3951 Aim: The aims of this study were on one hand, to evaluate the significance of achieving mole... more 3951 Aim: The aims of this study were on one hand, to evaluate the significance of achieving molecular response (MR) by fluorescent-PCR (F-PCR) of Ig genes in a prospective way, particularly in patients with singular…
One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS ... more One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show benefit from a second transplant. The aim of our study was to investigate the efficacy in terms of response improvement and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first high-dose procedure. Patients diagnosed with MM from Oct 1999 to Dec 2004 younger than 70 years received 6 courses of VBMCP/VBAD and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (second auto with CVB - cyclophosphamide, etoposide and BCNU - or MEL-200 intensification or an allo-RIC with Fludarabine/MEL-140 conditioning, if sibling donor available). Eighty-eight patients received a seco...
We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC... more We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology. Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional pr...
Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia... more Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia in patients over 60 years old. Results of the CETLAM AML-99 protocol Intensive induction and consolidationtherapy with agents such as idarubicin1,2and high-dose cytarabine3-6 and hema-topoietic stem cell transplantation7 are the mainstay in the treatment of acute myeloid leukemia (AML). However, while the inci-dence of AML increases with age, these treatments provide greater benefit to younger rather than to older patients. More than one half of the patients with AML are older than 60 years8 and, therefore, most are not candidates for intensive therapies because of co-morbid conditions or
For establishing the true effect of different response categories in patients with multiple myelo... more For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10−5); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are ali...
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Papers by Joan Besalduch