GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4702-4702
    Abstract: Abstract 4702 INTRODUCTION The allogeneic hematopoietic stem cell transplantation remains the only curative option for certain hematological malignancies. The use of reduced intensity conditioning (RIC) has diminished the transplant-related mortality, making it possible to consider this therapeutic option in elderly patients with associated morbidity. The graft versus host disease (GVHD) is a late-onset complication in this type of transplant which still remains one of the major causes of morbidity and mortality. Hematopoietic chimerism (HQ) levels related to relapse or GVHD in RIC allogeneic transplantation (allo-RIC) have not been established. We have studied the relationship between HQ and the incidence of GVHD and relapse, using real time-PCR for chimerism quantification. PATIENTS AND METHODS We evaluated 16 patients with hematological malignancies (11 AML, 3 ALL, 1 CLL, 1 plasma cell leukemia) undergoing allo-RIC in the last three years. The median follow up of this series was 310 days (range 86–958 days), with a median age of 53 years (range 26–64). A sibling donor was found in 11 cases (69%) and fourteen donors (88%) were HLA identical. Bone marrow was the source of progenitors in 12 cases, peripheral blood in 3 and umbilical cord in one. The conditioning regimen was: fludarabine + busulphan (44%), fludarabine + busulphan + timoglobulin (23%), fludarabine + melphalan (13%) and others (21%). GVHD prophylaxis was performed with cyclosporine A (CsA) + methotrexate (44%), CsA + mycophenolate (31%) and tacrolimus + syrolimus (19%). The HQ was studied in peripheral blood DNA at the time of granulocyte engraftment, and later 30, 45 and 60 days after stem cells infusion. Chimerism was expressed as a percentage of residual host cells. Quantitative real-time PCR amplification of null alleles or insertion/deletion polymorphisms was used for HQ analysis (Jimenez et al, 2005; Leukemia 2005; 19:336-43). Chimerism was expressed as a percentage of residual host cells. Chi-square test was employed to evaluate qLas variables cualitativas se analizaron mediante chi-cuadrado y se usaron test no paramétricos para las cuantitativas. ualitative variables and non-parametric tests for quantitative variables. El análisis multivariante fue realizado mediante regresión de Cox. The Kaplan-Meier model with log-rank test comparisons were applied for survival analysis. RESULTS The median time of engraftment was 16 days (12-27) for granulocytes and 18 days (10-69) for platelets. Ten patients (63%) developed acute GVHD (aGVHD), eight of them Grade II-IV. The incidence of late-onset aGVHD was 38%, with a mean time to appearance of 117 days (90-190). Six patients (38%) developed chronic GVHD (cGVHD), and in four cases a previous late-onset aGVHD had been recorded. In our series, disease relapse was observed in 6 patients (37.5%), whereas 7 patients died (3 infections, 2 progressive disease, 1 aGVHD and one bleeding). No relapse was found in the group of patient who developed cGVHD compared with 60% relapses in those without cGVHD (Fisher's exact test, p = 0.026). However, overall survival did not differ significantly in both groups. Median HQ at the time of granulocyte engraftment was 2,65% (0.07 to 55), on day +30 was 1.4% (0.01-12), on day +45 was 1.0% (0.01-9) and on day +60 1.7% (0.01-15). HQ showed significantly lower levels in those patients who did not relapsed either on day +30 (0.4% vs 4.0%, p= 0.016), on day +45 (0.35% vs 5.5%, p= 0.04), and on day +60 (0.4% vs 4.5%, p= 0.04). With respect to cGVHD, we observed a trend to lower HQ levels in those patients who developed cGVHD compared with those who did not develop it on day +30 (0.25% vs 1.9%, p= 0.056) and +45 (0.26% vs 1.7%, p= 0.066), but these results were at the limit of statistical significance. CONCLUSIONS Our data show that HQ levels may help us to identify a group of patients whith higher risk of relapse also in allo-RIC. The monitoring of HQ may also be useful to predict patients who will develop cGVHD after SCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3775-3775
    Abstract: Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3325-3325
    Abstract: INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (alloSCT) is the only curative strategy for relapsed/refractory T cell lymphoma (T-NHL). In the past ten years, there have been several improvements in conditioning regimens and graft versus host disease prophylaxis (GVHD), which have contributed to lower transplant-related mortality (TRM). Also, selective and low toxicity therapies, might improve response quality in some T-NHL Recently, haploidentical stem cell transplantation (Haplo) with post-transplant cyclophosphamide is a new option for those patients who do not have an HLA-identical sibling or a suitable unrelated donor, but also it has shortened the time for urgent cases. METHODS: This study analyzes overall outcomes of 211 consecutive patients diagnosed with T-NHL who received an alloSCT from 1995 to 2018 in GELTAMO/GETH centers. Previous therapies (chemotherapies and autologous stem cell transplantation) and baseline diagnostic parameters were recorded. RESULTS The median age at alloSCT was 47 years (range, 17-69). (see table 1). Forty-nine (23%) had primary extranodal disease. Disease status pre alloSCT was available in 202 patientes: 54% were in complete response (CR), 30% in partial response (PR) and 16% with stable/progressive disease (PD). Since 2013 BV was used as a bridge therapy in ≥ 3rd line in 25 patients with CD30+ tumor expression, it was effective in 20 (CR 68% (n=17), PR 12% (n=3) PD 16% (n=4), not assessed in 1 case). The use of BV was not associated with a better response probability pre alloSCT compared with other regimens used after third line and it did not impact on post alloSCT outcomes. Reduced intensity conditioning (RIC) was the most frequent (76%, n=156). (see table 2) GVHD prophylaxis were Methotrexate + CsaA or Tacrolimus (n=72, 35,8%), sirolimus-tacrolimus (n=37; 18,4%), Cy-post based (n=44, 21,9%; used in Haplo setting n= 29). The median follow-up of all cohort was 22.5 months (range, 0-280). The two year overall survival (OS) and disease free survival (DFS) were 60% (CI95%, 53-67%) and 76.7% (CI95%, 69.3-82.5%) (Figure 1A) We observed a significant improvement in alloSCT outcomes since 2011 (OS 〈 2011 51.4% vs ≥2011 64.8%, p=0,04).(Figure 1B) Disease status was the only pre alloSCT variable that impacts 2 years - OS: CR 72.8% (CI95%, 63-80.4%), PR 52%(38.7-63.7%), PD 43.8 (26.5-59.8%) (p=0.002) (Figure 1C). Forty-three (21%) cases relapsed after alloSCT. To analyze the impact of GVHD on OS and DFS we selected landmark time point at day +100 and +1 year after alloSCT for acute (aGVHD) and chronic GVHD (cGVHD) respectively, which allowed us to capture the majority of events that could interfere with the analysis. A landmark analysis (day +100) showed a 2 year OS for grade 3-4 aGVHD was 18% and for 1-2 aGVHD 54,6% (p 〈 0,001). The severity of aGVHD had no impact on DFS. Different grades of cGVHD did not impact OS nor DFS significantly. Cumulative incidence of acute GVHD at 90 days was 51.6% (CI95%, 43.9-58.2%) being 27% grade 3-4. Chronic GVHD at 6 months was 53.9% (46.1-60.5), 54% of cases were grade 3-4). The 2 years non relapse mortality (NRM) was 30.2% (CI95%, 23.3-36.5%); the main causes contributing to NRM were GVHD (40%) and infections (44%) Haploidentical (Haplo) alloSCT was introduced in 2012 (29 of 128). With a median follow up of 13 months (range, 0-60) we found that outcomes in terms of 1 year OS (Haplo 60.7% vs. others 67,5%), 1 year DFS (Haplo 74.8% vs. others 83.8%) and 1 year NRM (Haplo 29.7% vs. 26%) are similar to other alloSCT modalities (Figure 1D). Not additional analysis could be estimated due to the low number of population at risk for each category. CONCLUSION Overall outcomes of alloSCT for T-NHL have improved over time. Complete response pre alloSCT is the only determinant for OS. Haploidentical alloSCT is not significantly different from other approaches and should be considered as an alternative. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4408-4408
    Abstract: Different treatment guidelines suggest that advanced follicular lymphoma (AFL) subjects should be treated only when meeting criteria treatment, such as GELF, are present. Conversely, when absent the watch and wait (W & W) approach is recommended. However, in our country, we had the impression that in real life, a high percentage of patients without the above-mentioned criteria were treated. With the purpose of unravelling the medical approach of AFL patients at diagnosis and subsequent evolution, the Lymphoma Subcommittee of the Argentinian Society of Haematology undertook this retrospective survey. Results: From years 2006 to 2014 305 patients from 23 institutions were included. GELF criteria were encountered in 62% of patients at diagnosis and all of them were treated with immunochemotherapy (ICT). Among the 116 (38%) patients without meeting GELF criteria (GELF negative group), in only 30 (26%) W & W was the approach chosen, while the rest received ICT. The survey questionnaire revealed that own assessment of the treating physician was the main reason for treating the GELF negative group. In the W & W group, 60% required ICT at a mean of 17 months, being 15% of them transformed to DLBCL at time of treatment. The 89% of cases (271/305) received ICT at some time; 66% R-CHOP, 29% R-CVP, and 5% other regimes. Patient median age receiving R-CHOP and R-CVP was 57 and 62 years (p 〈 .01), respectively. Rituximab maintenance (RM) was added to ICT in 64% of cases. For the whole group, with a median follow up of 36 months, the overall survival (OS) was 95% and progression free survival (PFS) 68%. Comparing GELF negative and positive groups, PFS was better for GELF negative group, 87% vs 61% (p 〈 .01). There was no difference in OS. Within the GELF negative group, OS was not different between patients treated at the time of diagnosis vs those in which a W & W approach was chosen. Conclusion: 1) When comparing with international reports, the percentage (62%) of patients with positive GELF criteria was higher at diagnosis. This fact may be due to delay in access to health care; 2) we found a remarkable discrepancy among guidelines recommendations and real life medical behaviour. Three out of four patients received treatment at diagnosis, when W & W ought to have been the guideline-recommended approach; 3) R-CHOP was the most used ICT scheme, while R-CVP was mostly reserved for the elderly. RM was indicated in the majority of patients, particularly after year 2011; 4) despite acknowledging the methodological limitations of this retrospective analysis, a high tumor mass (GELF positive) picture conferred a worse prognosis in term of PFS, while a W & W approach did not affect the OS for the GELF negative group. Disclosures Riveros: Roche: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 311-311
    Abstract: Background and Objectives: Following cord blood transplants (CBT) there is a period of severe and often prolonged immune deficiency that results in long term susceptibility to infections. Immune reconstitution is an important factor for long term survival. We analyzed the immune reconstitution of adult recipients of a single unit CBTs supported by a low number of third party donor highly purified mobilized hematopoietic stem cells (dual CB/TPD transplants), as previously described (Magro et al. Haematologica2006;91:640–8). This strategy results in transient double chimerism of CB and TPD cells and early granulocyte recovery, initially of TPD predominance. Complete CB chimerism is regularly achieved within 100 days.The objective of this study is to evaluate immune reconstitution in this CBT. Patients and Methods: Data were obtained from 19 patients between July 2004 and July 2006. Data collection was initiated at different intervals (from day −7 to +720, quartiles Q1=35, Q2=90 and Q3=210). Samples were obtained on days +15, +35, +55, +90 and monthly thereafter up to two years. By four-color flow cytometric immunophenotyping we analyzed the subsets of peripheral blood lymphocytes: CD3+/CD4+ (T helper/inducer), CD3+/CD8+ (T suppressor/cytotoxic), NK cells (CD3−/CD56+/CD16+) and B cells, as well as cells with naïve, memory and effector T-cell immunophenotypes. TREC bearing cells were analyzed by quantitative PCR in sorted CD4+ and CD8+ T cells collected from 3 months post-transplant onwards. Results: CD56+ cells recovered early after transplantation, with median absolute number counts (ANC) of 69 (range 18–307), 170 (0–366) and 159 (32–531) cells/uL in days +15, +35 and +55 samples [normal controls 153 (71–438)], representing the largest subset within the first two months (decreasing proportions of 60%, 50% and 40%, respectively). ANC of CD4 and CD8 T cells remained low for several months, progressively increasing to reach normal ranges at different intervals. Naïve CD4 and CD8 cells (CD45RO−/CD27+) start to be detected by immunophenotyping after three months post-transplantation with median ANC of 17 (12–79) and 12 (5–103) cells/uL respectively and increasing thereafter [normal controls 860 (552–1072) and 331 (227–521)] . By the end of the first year values of T cell subsets were: CD4+, 823 (16–1123) cells/uL [normal controls 872 (470–1093)]; CD8 934 (56–1174) [normal controls 371 (208–808)] , with persisting predominance of the naive phenotypes and proportions of memory phenotypes slowly increasing. B cells became detectable around day +90 with median ANC of 249 (0–1934) cells/uL, rapidly reaching values within the normal range [275 (133–684)]. Transient acute GVHD was developed by six of the 19 patients. All showed a transient drop in absolute numbers of NK, T and B cells. Chimerism analysis showed initial transient double chimerism of CB and TPD cells. Complete CB chimerism was achieved between days +15 and +94 (median, +35). Results of chimerism of lymphocyte subsets and TREC are not yet available. Conclusions: Following dual CB/TPD transplants we have observed early recovery of NK and B-cells and slow development of T cells subsets and of non-naive immunophenotypes.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...