There is an ongoing debate on whether a drought induced carbohydrate limitation (source limitation) or a direct effect of water shortage (sink limitation) limit growth under drought. In this study, ...we investigated the effects of the two driest summers recorded in southern Chile in the last seven decades, on the growth and non-structural carbohydrates (NSC) concentrations of the slow-growing conifer Fitzroya cupressoides. Specifically, we studied the seasonal variation of NSC in saplings and adults one and two years after the occurrence of a 2 year-summer drought at two sites of contrasting precipitation and productivity (mesic-productive vs. rainy-less productive). We also evaluated radial growth before, during and after the drought, and predicted that drought could have reduced growth. If drought caused C source limitation, we expected that NSCs will be lower during the first than the second year after drought. Conversely, similar NSC concentrations between years or higher NSC concentrations in the first year would be supportive of sink limitation. Also, due to the lower biomass of saplings compared with adults, we expected that saplings should experience stronger seasonal NSC remobilization than adults. We confirmed this last expectation. Moreover, we found no significant growth reduction during drought in the rainy site and a slightly significant growth reduction at the mesic site for both saplings and adults. Across organs and in both sites and age classes, NSC, starch, and sugar concentrations were generally higher in the first than in the second year following drought, while NSC seasonal remobilization was generally lower. Higher NSC concentrations along with lower seasonal NSC remobilization during the first post-drought year are supportive of sink limitation. However, as these results were found at both sites while growth decreased slightly and just at the mesic site, limited growth only is unlikely to have caused NSC accumulation. Rather, these results suggest that the post-drought dynamics of carbohydrate storage are partly decoupled from the growth dynamics, and that the rebuild of C reserves after drought may be a priority in this species.
Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the ...treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.
Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity.
To characterize patients with AL amyloidosis in Chilean public health centers.
We conducted a retrospective, ...multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated.
Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%.
It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.
Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged ...the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children's Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program.
To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation.
Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests.
Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively.
LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.
Background Multiple myeloma (MM) is a heterogeneous disease that is most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the young population are ...scarce and it is recognized that it remains incurable even in this group of patients. We present here the outcomes of patients under 40 years old cohort in Latin-American countries. On behalf of GELAMM (Grupo de Estudio Latino-Americano de Mieloma Múltiple).
Methods Retrospective international multicenter cohort study. We analyzed MM patients under 40 years old who received treatment in 6 Latin-American countries, between 2010 and 2018. Demographics and disease features were analyzed using descriptive statics. We examined treatment characteristics and response rates. The overall survival (OS) of the entire cohort was analyzed using Kaplan-Meier curves.
Results Eighty-six patients of 6 countries were analyzed (Table1). The mean age was 35.4 years old, and 60% were male. The most frequent monoclonal component type was IgG followed by light chain MM. Risk determined by ISS was distributed in almost equal percentages. The most frequent cytogenetic alteration was the t (4;14) that was found in four patients out of 25 evaluated. The missing data were greater than 70%. Skeleton-related events were the most frequent clinical feature, followed by anemia and renal failure. Plasmacytomas and fractures were present in more than 20 percent of cases.
With regard to treatment, VCD / CyBorD was the most used regimen, followed by VTD. The overall response rate (ORR) was 63%. Fifty-three patients received high dose therapy and autologous stem cell transplantation (62%). Only 8% received post-transplant consolidation, and 45% received maintenance therapy.
The median OS of the entire cohort was 45 months, and a plateau in the survival curve was not observed, suggesting that patients continue relapsing over the time.
Conclusion In this Latin American multicenter study, we found that the young population with MM has similar presentation characteristics to those of elderly patients. A significant amount of information is lost regarding the risk characterization, especially in regard with cytogenetics. With respect to treatment, less than half of the patients achieve very good partial response or better. It is striking that more than a third of this young patients did not access to high doses of chemotherapy and bone marrow transplantation. Maintenance therapy is offered to less than half patients. The median OS is lower than in other series of patients younger than 40 years, even than in the elderly cohorts. Prospective multicentric studies are required to elucidate the behavior of the disease in this group of patients.
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Peña:Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights. Rojas:Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau.
Background
Multiple myeloma (MM) is a frequent hematologic malignancy. The current gold standard frontline strategy includes a proteasome inhibitor (PI)-based induction, followed by autologous stem ...cell transplant (ASCT).
Access to novel drugs in Latin America (LA) is limited. ASCT is available in most countries, but real access to it is highly heterogeneous. Data regarding patients´ outcomes in candidates to ASCT in the region is scarce.
The aim of this study was to describe clinical characteristics and outcomes of MM transplant eligible patients in LA countries.
Material and Methods
Retrospective international multicenter cohort study. Consecutive MM transplant- eligible patients diagnosed between 2010 and 2018 from participating centers in Chile, Argentina, Ecuador, Mexico, Colombia, and Uruguay were included. Data were collected from clinical records in a standardized report form. We analyzed clinical characteristics at diagnosis and frontline therapy outcomes, including ASCT.
Transplant-eligible patients were defined as fit patients younger than 66 years old.
Active MM and response to treatment were defined according to current IMWG criteria.
Inclusion criteria:
1.- Patients with newly diagnosed active MM between 2010 and 2018.
2.- Older than 18 years, and younger than 66 years.
3- Candidates for ASCT according to the evaluation of the attending physician
Exclusion criteria:
1- Lack of minimum data in the clinical history
2- Plasma cell leukemia, AL amyloidosis or solitary plasmacytoma.
3- HIV infection
4-No consent and/or Ethics Committee approvals.
Statistical analysis
A descriptive statistic has been done. Comparisons of characteristics between groups was made usingT-student, Chi2 or ANOVA, as appropriate. Survival analysis was performed using Kaplan-Meier curves. Comparisons of survival between groups were made by the logarithmic recording method and the calculations of the risk relationships by Cox regression.
Statistical analysis was performed by using STATA 13.
Results
We included 1293 patients in the study, 363 from Chile, 395 from Argentina, 209 from Colombia, 45 from Ecuador, 151 from Mexico, and 130 from Uruguay. The main characteristics at diagnosis and therapeutic strategies are shown in Table 1. Optimal response (sCR, CR and VGPR) was achieved in 38% of the patients in the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) group, in 46% in the bortezomib, thalidomide, and dexamethasone (VTD) group, and in 36% in the cyclophosphamide, thalidomide, and dexamethasone (CTD) group, the 3 main induction regimens used. Only 53% of patients finally received ASCT.
Significant differences were found between both groups, private and public institutions, regarding burden of symptoms, ISS staging, access to PI based induction, ASCT completion and adequate maintenance, with patients from the latter being more symptomatic, and receiving suboptimal therapy.
FISH analysis was performed in less than 50% of patients, both in the public and private setting.
With a median follow up of 34 months (range 1-113), median overall survival (OS) was 86 months. The 5-year progression free survival (PFS) was 38% and 5- year overall survival (OS) was 64%. When comparing public vs private settings, 5 year OS was 45% vs 80%, with a median OS of 56 months vs not reached, respectively (P<0,0001).
In the multivariable analysis renal failure (p=0.03), achieving less than VGPR response (p<0.0001), not undergoing ASCT (p=0.001), and not receiving maintenance (p=0.005) were independent factors associated with worse outcome.
Conclusion
This is the largest report on transplant eligible patients with MM in LA. Great inequities are shown between public and private health systems.
Survival in transplant-eligible patients is lower than that described in other regions.
Only one third of patients had FISH performed. This means that very few patients are treated with a risk-based induction in LA.
Patients in the public setting are diagnosed with a more symptomatic disease, probably due to a late diagnosis. OS is significantly worse in the public setting. This might be explained by the significant differences in access to PI-based induction, ASCT and maintenance between private and public institutions, with patients from the latter receiving suboptimal frontline therapy and maintenance.
Reasons for 47% of potential candidates not being transplanted merit further analysis.
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Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.
Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the ...Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had one alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation was performed in 36 cases, 20 patients did not use this consolidative strategy, and this data was missed in three cases.
Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (p=0.029), consolidation with ASCT (p<0.001), and maintenance therapy (p=0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, p<0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.
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