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In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 7, No. S1 ( 2017-1)

Type of Medium: Online Resource

ISSN: 2110-5820

URL: Article

DOI: 10.1186/s13613-016-0224-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2617094-2

In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5285-5285

Abstract: When patients with hematological malignancies develop a life-threatening complication there may be reluctance to admit them in intensive care units (ICU) because of their supposed poor prognosis. The objective of this study was to evaluate the mortality during the ICU admission, the long-term survival, and the prognostic factors that contribute to the survival of patients with hematological malignancies who were transferred to ICU due to a life-threatening complication. From January 2000 to May 2004, the variables at admission and during stay at the ICU, and the follow-up were reviwed in 58 consecutive critically-ill patients with a hematological malignancy from a single institution. The median age (range) was 55 (15–75) years and the male/female ratio was: 38/20. The hematological underlying diseases were: NHL (18 patients), AML (10), ALL (9), MM (6), chronic lymphoproliferative disorder (5), chronic myeloproliferative disorder (4), myelodysplastic syndrome (3), aplastic anemia (2) and Hodgkin’s lymphoma (1). Seven patients had received a hematopoietic stem cell transplant prior to the ICU admission. The main life-threatening acute illness precipitating the ICU transfer were: septic shock (26 patients, 45%), respiratory failure (21, 36%), non-septic hemodynamic instability (5, 9%), respiratory arrest related to a neurological event (2, 3%), post-surgical status (2, 3%), cardiac infarction (1, 2%) and polytrauma (1, 2%). Twenty-one patients (36%) could be discharged alive from the ICU. The median overall survival (range) for ICU discharged patients was 23 (0–54) months, with a median follow-up of 8 months. The actuarial probability of discharged patients to be alive was 56% (CI 95%: 31–75) at 6 months, and a 48% (CI 95%: 13–70) at 12 months. The mean Acute Physiology and Chronic Health Evaluation II (APACHE) score at admission, neutropenia, need for mechanical ventilation, maximum FIO2 requirements at 24 hours from admission, presence of septic shock, renal impairment or liver damage, were associated with a poor outcome in the univariate analysis. A documented infection was not associated with a higher mortality rate except for fungal infection. The APACHE II score at 48 and 72 hours of ICU admission decreased both in surviving and non-surviving patients due to therapeutic manoeuvres and was not predictive of the outcome. The type of the hematological malignancy, its prognosis and the presence of active disease at ICU admission did not predict patients outcome in our series. The number of failing organs also predicted a poorer survival for patients with more than two failing organs (p=0.038). In a multivariate logistical regression model, only the cardiovascular failure requiring vasoactive and the need of mechanical ventilation predicted outcome in the ICU admitted patients diagnosed with a hematological malignancy. A high proportion of admitted patients with a life-threatening complication and a hematological malignancy could be discharged from ICU. Although the mortality rate immediately after ICU discharge was high, those patients that survived the first week outside ICU had an expected survival only conditioned by their hematological malignancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V104.11.5285.5285

Language: English

Publisher: American Society of Hematology

Publication Date: 2004

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1936-1936

Abstract: Abstract 1936 Background and aims: Graft-failure (GF) is an infrequent and poor complication of allogeneic stem cell transplantation (SCT). Strategies for reversing GF will depend on the options available in each situation. Patients and Methods: A questionnaire about GF was sent to all centers of the Grupo Español de Trasplante Hematopoyético (GETH). Fourteen Spanish institutions reported their GF from January 2006 to October 2010. Primary GF was defined as ANC 〉 0.5×109/L not reached for three consecutive days by day +28 after SCT from peripheral blood (PB) or bone marrow (BM) progenitors and by day +60 after SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a recurrent ANC 〈 0.5×109/L for at least 7days. Results: Eighty patients with GF were reported (median age 34 yr. [range: 1–68]; 54M/26F). Basal diseases were AML 30 (38%), ALL 14 (17%), lymphoproliferative disorder 12 (15%), myelodysplastic syndromes 9 (11%), myeloproliferative syndromes 7 (9%), aplastic anemia 5 (6%), and congenital disorders 3 (4%). Status of the neoplastic disease was: 1st/2nd CR or 1st chronic phase in 50 (62%) patients and 〉 2nd CR or active disease in 30 (38%) patients. Conditioning therapy for 1st SCT was myeloablative in 45 (56%) and non-myeloablative in 35 (44%) patients. Donors were related in 35 (44%) and unrelated in 45 (56%). Progenitors were from mobilized PB in 45 (56%), UCB in 26 (33%) and BM in 9 (11%). At the time of GF, chimerism status (n=75) was donor complete in 6 (8%), mixed in 28 (35%) and from the patient in 41 (55%) individuals. Forty-five (56%) and 35 (44%) patients presented primary and secondary GF. Seventy-one patients received a second SCT from the same donor (31 patients [44%]), from a different donor (35 patients [49%] ) or an autologous back-up (5 patients [7%]). The most frequent conditioning regimens (n=65) in second allogeneic stem cell infusion were fludarabine+ thymoglobulin (ATG) (19 [29%] ), anti-lymphocyte immunoglobulin alone (9 [14%]) and cyclophosphamide+ATG (6 [9%] ). ATG or alemtuzumab were used in 52 patients (80%) as part of the preparative regimen. Progenitors were from mobilized PB in 52 (79%), UCB in 8 (12%) and BM in 6 (9%) patients. Eleven (20%) and 2 (4%) out of 55 evaluable patients presented again primary or secondary GF. The median survival time from GF was 12 months [range: 1–23].The 5-yr. probability of survival was 28% (95%CI: 14%–42%) with a median follow-up for alive patients of 27 months [range: 1–103] . The 5-yr. non-relapse mortality was 47% [35%–59%]. There was a trend for a better survival in patients under 18 years-old. No other factors such as graft source, in vivo T-cell depletion or the conditioning regimen influenced on patient's survival. By competing risk estimation, the transplant-related mortality and the relapse probability at 5 years in the 66 patients that received a second transplant were 51% [95%CI: 38% – 63%] and 24% [95%CI: 10% – 41%]. Conclusions: The prognosis of GF after allogeneic SCT was poor, although some patients presented long survival if successful recovery of GF was obtained. The strategy adopted to treat GF has been heterogeneous. Younger age showed a trend for better survival in this series. Supported by grants P-EF/10 from FIJC and RD06/0020/1056 from RETICC. Disclosures: Sanz: Novartis: Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.1936.1936

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1168-1168

Abstract: Abstract 1168 Poster Board I-190 Intravenous ganciclovir (iv-Gcv) is the standard drug for pre-emptive therapy of citomegalovirus (CMV) infection in allogeneic stem cell (allo-SCT) patients. Valganciclovir (Vgcv), an oral prodrug of ganciclovir, is used very often in practice although there is no approved indication for this specific use. Methods: We performed a prospective phase II multicentric study with Vgcv in adult patients to evaluate its efficacy and safety in the pre-emptive treatment of CMV-Ag or DNAemia within the first 180 days after SCT (ClinicalTrials.gov Identifier: NCT00386412). The results were compared with those obtained with iv-GCV in a retrospective control group. The primary study endpoint (success) was the achievement of negative CMV-AG/PCR on day 14 of treatment without changing the protocol antiviral (Vgcv or iv-gcv). Secondary end-points were negative CMV-AG/PCR, rate of neutropenia ( 〈 500 neutrophils/mm3) and nephrotoxicity, until 35 days after the beginning of treatment. A minimum patient weight of 50 kg was required. Vgcv was given at 900 mg/12h for 14 days (induction therapy) followed by 900 mg/day for another 14 days (maintenance treatment), in both cases adjusted according to renal function. If CMV was positive at day +21, the treatment was considered a failure and Vgcv was stopped. Patients: Here we presented the final results on 90 patients (60 prospective treated with Vgcv and 30 treated with iv-Gcv). There were no differences between Vgcv and iv-Gcv groups in median age (47 vs 49 years), median weight (72,5 vs 62kg), type of donor (55% vs 37% HLA identical siblings, 43% vs 56% unrelated and 2% vs 7% related mismatch), and conditioning regimen (mieloablative 42% vs 57%; reduced intensity in 58% vs 43%). More iv-Gcv patients had acute GVHD II-IV at CMV viremia presentation (12% vs 42%). The majority of the patients where receiving immunosuppression at CMV viremia presentation (97% vs 97%). Median time for CMV-Ag/PCR positivity was 46 days after SCT for both groups. Results: Two patients developed CMV disease during antiviral therapy: one in the Vgcv group (a proved gastric on day +9 of therapy) and one in the iv-gcv group. At 2 months of follow-up no more cases of CMV disease were diagnosed. Nuetropenia ( 〈 500/mm3): 8 cases in Vgcv group (13.3%) vs 1 case in iv-gcv group (3.3%) (P ns). Only one patient in the iv-gcv group developed nephrotoxicity. Comments: Oral valganciclovir therapy given at a fixed dose in patients over 50 kg for the pre-emptive therapy of CMV in allogeneic patients was effective and with similar toxicity compared with iv-gcv. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.1168.1168

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1382-1382

Abstract: Abstract 1382 The effectiveness of rituximab maintenance in the treatment of CLL has been investigated in a phase II clinical trial that includes two treatment parts. First, patients were given R-FCM up to 6 cycles as induction therapy, achieving an overall response rate of 93% and 46% of CR with negative minimal residual disease (MRD) (Bosch et al. JCO, etc). Second, three months after concluding R-FCM, patients having achieved CR or PR receive rituximab maintenance (375 mg/m2) every three months for two years (up to 8 cycles). We present here the preliminary results of the second part of the study, namely the efficacy of rituximab maintenance. Evaluation of response was performed three months after the last cycle of maintenance and included bone marrow (BM) examination, MRD assessment in peripheral blood and BM by four-color flow cytometry. Patients in whom rituximab maintenance was prematurely interrupted due to toxicity were considered as failures. Fifty-six patients (median age 60 years, 70% female) responding to R-FCM were evaluable for response to rituximab maintenance. Median number of cycles of maintenance given was 8 (range, 3 to 8), 77% of patients completed the entire planned treatment, whereas 91% received 6 or more cycles. Treatment was delayed due to insufficient hematological recovery in 12 cycles (2.7%). Toxicity was mainly hematological, with neutropenia being observed in 31.8% of cycles (Grade 3 & 4 in 8.9%), thrombocytopenia in 3.4% and anemia in 3.9%. Hypogammaglobulinemia occurred in 38% of patients (low levels of IgA in 50%, IgG in 34%, and IgM in 60%). Eight patients, three of them with hypogammaglobulinemia, experienced grade 3 & 4 infectious episodes (4 pneumonia, 2 gastrointestinal, 1 myositis, and 1 cerebral abscess). Herpes virus (I/VZ) reactivation was observed in 8 patients. Two patients died due to multifocal leukoencephalopathy and hemophagocytic syndrome, respectively. After rituximab maintenance, 44.6% of patients were in CR MRD negative, 41% in CR, 3.6% in PR, and 10.7% failed to treatment. Failures were due to disease progression (two patients), development of severe neutropenia (two patients), and death (two patients). Among 28 patients that were in CR MRD (-) at the onset of the maintenance part, 19 held the MRD negative status at the end of maintenance, 5 (18%) turned negative into positive MRD (probability of conversion, 40% at 30 months), whereas 4 failed to treatment (2 neutropenia, 1 progression, 1 death). Moreover, 5 of 24 patients (22%) in CR MRD(+) after R-FCM became MRD negative after rituximab maintenance, 17 maintained the CR, one patient achieved a PR, and one patient progressed under maintenance (Table 1). In conclusion, rituximab maintenance after chemoimmunotherapy seems to prolong duration of response and, in some cases, improves the quality of response towards a CR with negative MRD. Maintenance with rituximab had the major benefit in patients in CR with positive MRD. The exact role and the best dosage and treatment schedule of rituximab as maintenance therapy in CLL should be now investigated in randomized clinical trials. Disclosures: Bosch: Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia. Garcia-Marco:ROCHE: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.1382.1382

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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

URL: Article

DOI: 10.1182/blood-2019-126507

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1561-1561

Abstract: Introduction: The BCL-2 inhibitor venetoclax (Ven) has been approved on monotherapy or combined with rituximab in relapsed/refractory CLL patients (pts) and combined with obinutuzumab in previously untreated CLL pts. However, evidence from clinical trials can be difficult to generalize to real-world patient populations. The VENARES study assesses the real-world use of Ven following approval to inform of subpopulations underrepresented in clinical trials. Methods: This is Spanish non-interventional retrospective, multicenter post-marketing observational study. The main objective was to evaluate the effectiveness of Ven in adult CLL pts by the overall response rate (ORR) at 9 months (mo) after the first Ven dose administration. Secondary objective was to evaluate the effectiveness for the Ven monotherapy and the Ven combined with rituximab subpopulations. Consecutive adult pts with diagnosis of CLL who have initiated Ven at least 9 mo before the inclusion in the study were included. Data of pts are retrospectively reviewed until the date of last follow-up or death. Results: 125 pts diagnosed with CLL and who met the eligibility criteria were analyzed. The median age was 72 years (67 - 77) with 76.8% being older than 65 years. Most patients were male (68.8%), had a concurrent disease (65.6%). ECOG PS was recorded in 76 pts: 40 pts (32%) had PS 0, 30 pts (24%) PS 1 and 6 pts (4.8%) PS 2. Pts had received a median of 4 prior lines of therapy (range 1-13 lines). At baseline, among the 92 pts with known Binet stage, 31 (33.7%) had stage C and 38 (41.3%) had stage B; bulky nodes ≥ 5 cm were present in 20 of 87 pts; 49 pts (39.2%) had an absolute lymphocyte count ≥ 25 x 10 9/L and 33 of 54 pts (61%) baseline beta-2 microglobulin value above of 3500 ng/mL. In total, 29 of 90 patients (32%) assessed had Cr 17p deletion, 28 of 86 patients (32%) tested had TP53 mutations, and 46 of 56 patients (82%) who were tested had unmutated immunoglobulin heavy-chain variable (IGHV) status. Ven was administered as monotherapy in 71 pts (57.6%), combined with rituximab in 36 pts (28.8%), combined with obinutuzumab in 5 pts (4%) and combined with other drugs in 13 pts (10.4%). 83 of 125 patients included were evaluable for the primary objective of the study: the ORR at 9 mo was 84.3% (70 patients): CR/CRi in 44 (53%) pts, PR/nPR in 26 pts (31.3%), SD in 9 pts (10.8%) and PD in 4 pts (4.8%). By treatment, in the evaluable patients, ORR at 9 months were 79.2% (38 of 48 patients) in the Ven monotherapy group, with 45% of CR/CRi, and 92.3% (24 of 26 patients) in the Ven combined with rituximab, with 61% CR/Cri. The median duration of PFS was not reached at the time of the analysis (1-June-2021). Kaplan-Meier estimates of the probability of PFS at 24 mo was 75.4% (95% CI, 58.2 - 86.3). Disease progression occurred in 21 pts. Assessment of minimal residual disease (MRD) was available for 32 patients (25.6%) on the basis of peripheral-blood samples, bone marrow or both. Best undetectable MRD was reached in fourteen patients (43.8%). uMRD was more common in pts treated with Ven combined with R (83.3%, 5 of 6 pts) than in pts treated with Ven monotherapy (33.3%, 7 of 21 pts). Adverse events (AEs) were reported during Ven therapy in all 125 patients, 93 of these pts reported AEs related to Ven. Related to Ven, 67 patients (53.6%) experienced at least one AE: 52 pts (41.6%) had neutropenia being grade 3 and 4 in 22 (42.3%) and 9 (17.3%) pts, respectively. 9 pts (7.2%) had febrile neutropenia. Thrombocytopenia and anemia were less common occurring in 5.6% and 2.4%, respectively. Tumor lysis syndrome (TLS) occurred in 4 of 125 pts during ramp-up (3 laboratory and 1 clinical), 2 of them were related to Ven both lab TLS. None of the pts discontinued therapy due to TLS. Richter transformation was observed in 6 pts (4.8%). Other common AEs was diarrhea (10.4%), but most cases were mild. Conclusions: Our first real-world data show that Ven monotherapy or combined with rituximab is effective in highly pre-treated CLL patients, ORR at 9 mo was 84.3% in all population and PFS estimate at 24 mo was 75.4% with similar outcomes to those in the pivotal clinical trials. The safety profile of Ven was consistent with prior experience of Ven in monotherapy or combined with rituximab and no new safety signals were detected. Disclosures Baltasar: Janssen, Abbvie: Consultancy. Terol: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; BMS: Consultancy; Roche: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Hospital Clinico Valencia: Current Employment. Moreno: Janssen, Abbvie: Research Funding; Abbvie, Janssen, AstraZeneca: Speakers Bureau; Abbvie, Janssen, AstraZeneca, Beigene: Membership on an entity's Board of Directors or advisory committees. Osorio: Janssen, Abbvie, Roche: Consultancy. De la Cruz: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirkin: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de la Serna: AbbVie, AstraZeneca, Roche: Speakers Bureau; ABBVIE, ASTRAZENECA,ROCHE: Research Funding; AbbVie, AstraZeneca, Beigene, Gilead, GSK, Janssen, Jazzpharma, Novartis, Roche: Consultancy. Arguiñano: Takeda, Sanofi, Janssen, BMS-Celgene, Abbvie: Speakers Bureau; Takeda, Sanofi, Janssen, BMS-Celgene, Abbvie: Consultancy. Loscertales: Janssen, Abbvie, Roche, Gilead: Speakers Bureau; Janssen, Abbvie, Astra-Zeneca, Beigene, Roche, Gilead: Consultancy. García: Janssen, Roche, Gilead, Celgene: Consultancy; Janssen, AbbVie: Research Funding; Janssen, Roche, Gilead, AbbVie, Celgene: Other: medical meetings funding. Pérez Persona: BMS/Celgene: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau; Amgen: Consultancy, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Speakers Bureau; AbbVie: Other: Support for attending meetings and/or travel, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; GSK: Consultancy; Incyte: Consultancy. Pérez-Encinas: Janssen: Consultancy. Caballero: Celgene, Janssen, Novartis, Abbvie: Speakers Bureau; Celgene, Janssen, Amgen: Consultancy. Ruiz-Zorrilla: Abbvie: Current Employment. Moreno: abbvie: Current Employment. Ferrà: Janssen, Roche, Gilead, Takeda, Abbvie: Consultancy; Janssen, Roche, Gilead, AbbVie: Other: medical meetings funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-147685

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3292-3292

Abstract: Introduction DLIs represent a major therapeutic approach for relapse and mixed chimerism (MC) after allogeneic hematopoietic cell transplant (AlloHCT). DLI studies have identified several variables with impact on response and GvHD. Despite some studies having explored the role of T-cells and other cell subsets, such as mononuclear cells (MNCs), comprehensive data regarding the cellular composition of DLI and its role in GvHD remains incomplete, as the development of GvHD post DLI is often unpredictable. Herein we analyzed the cellular composition of DLI from fully human leukocyte antigen (HLA) identical sibling (HLA Id Sib) donors and its impact on the development of GvHD in patients who underwent AlloHCT for hematological malignancy, and its impact on the development of GvHD. Methods Inclusion criteria were as follows: 1) Patients ≥ 18 years-old, 2) AlloHCT, 3) HLA Id Sib donor; 4) treatment with DLI; and 5) signed informed consent of patient and donor. Exclusion criteria were: 1) unrelated or mismatched related donors, 2) HCT2 prior to DLI, or 3) GvHD at DLI. For the purpose of avoiding bias, only the cell composition of the first DLI (DLI1) was analyzed. The following cell subsets of the DLI were studied: CD3+, CD4+, CD8+, CD16+CD56+CD3+ (NKT-cell), CD3+CD45RA+CCR7+ (TN), CD3+CD45RA+CCR7+CD31+ (TRTE), CD3+CD45RA+CD95+CD27+ (TSCM), CD3+CD45RA-CCR7+ (TCM), CD3+CD45RA-CCR7- (TEM), CD3+CD45RA+CCR7- (TTE), CD3+CD4+CD25brightCD127dim (TREG), CD3+CD4+CD25brightCD45RA+CD127dim (naïve TREG). The TN, TCM, TEM and TEM compartment was analyzed for both CD4+ and CD8+. We also analyzed the MNCs, CD19+ (B-cell), CD27+CD19+ (mature B-cell), CD16+CD56+CD27- (natural killer (NK+) cell) and CD16+CD56+CD27+ (CD27+NK+cell). Results Fifty-six DLIs were infused in 36 patients; the median number of DLI was 1 per patient (range, 1-3). Diagnoses were as follows: 13 AML/MDS, 6 HL, 5 MPN, 4 NHL, 4 CLL, 3 MM and 1 B-ALL. For the study, a landmark analysis was performed from the DLI date. The median follow up from DLI was 282 days (range, 9-5,560 days). Overall response rate in relapsed patients was 29% (9 of 31 patients; 6 CR and 3 PR, most responses being observed after DLI1. Further, five patients had DLI for MC and full donor chimerism was achieved in all patients. Thirteen patients (36%) developed GvHD post DLI. Two patients had GvHD before DLI, but there was no case of GvHD at DLI. The median time interval form DLI to GvHD was 76 days (range, 7-261). As per clinical presentation, 10 patients (27%) had acute GvHD, whereas eight patients (22%) had chronic GvHD. The 6-month and 1-year cumulative incidence (CI) of GvHD was 33% and 46%, respectively. When the risk of GvHD was analyzed according to DLI cell subsets, we observed that a DLI1 containing 〉 3x106 CD8+TN correlated with an increased incidence of GvHD (Figure 1a). Also, a DLI1 with 〉 0.8x108 MNCs/Kg (Figure 1b), 〉 2.6x106 mature B-cell/Kg, or 〉 0.35x106 CD27+NK+cells/Kg were linked to the development of GvHD (Table 1). Noteworthy, CD3+, TN (both CD4+ and CD8+ combined) or CD4+TN had no impact on the development of GvHD; and a high proportion of TREG was not protective for the development of GvHD (Table 2). Finally, there was no statistically significant association between any clinical variable and GvHD. Conclusion In conclusion, in this cohort of AlloHCT patients from HLA Id Sib donors, a DLI1 containing a high proportion of CD8+TN, but not CD4+TN, increased the probability of developing GvHD. Further, a DLI1 containing a high dose of MNCs, CD27+NK+cells and mature B-cell also associated with GvHD. These data provide novel insight for the understanding of GvHD post DLI. A DLI1 containing a lower dose of CD8+TN could reduce the risk of GvHD, but this asset warrants further validation in larger cohorts, and within a controlled randomized trial setting. Disclosures Bosch: F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124358

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 618-618

Abstract: High transplant-related mortality (TRM) is of major concern after myeloablative conditioning for UCBT. The use of once-daily IV BU and FLU has recently shown to reduce TRM and prolong disease-free survival (DFS) in patients with myeloid malignancies undergoing transplantation from HLA-identical siblings and marrow unrelated donors. The aim of this study of the GETH cooperative group was to evaluate the short term outcome of single-unit UCBT for the treatment of patients with high-risk hematologic malignancies after conditioning with TT, once-daily IV BU, FLU and rabbit ATG. Seventy-three consecutive patients (37 males, 36 females) with a median age of 31 yr (range, 1–54; 67 adults) who underwent transplantation from March 2005 to March 2007 were included. Conditioning consisted of TT (5 mg/kg/d on days -7 and -6), FLU (50 mg/m2/d on days −5, −4, and −3), once-daily IV BU (3.2 mg/kg on days −5, −4, and −3) and Thymoglobulin (2 mg/kg/d on days −5, −4, −3, and −2). Cyclosporine and prednisone were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (92%) received an HLA-mismatched UCB unit with 1 (36%) or 2 (56%) HLA disparities. The median number of nucleated and CD34+ cells infused was 2.5 x 107/kg and 1.4 x 105/kg respectively. Baseline diagnosis was AML (32 pts), ALL (29), MDS (4), Hodgkin’s disease (4), NHL (3), and CML (1). Fifty-three patients (73%) were on early disease stage at transplant (acute leukemia and lymphoma in CR1 or CR2, MDS untreated or in CR, and CML in CP) and 15 (20%) had failed a previous autologous stem cell transplant (ASCT). Cumulative incidence (CI) of myeloid and platelet engraftment was 89% and 64% (Kaplan-Meier cumulative probability, 100% and 75%) at a median time of 22 (range, 11–52) and 41 (range, 24–115) days respectively. CI of grades II-IV and III-IV acute GVHD was 16% and 6% respectively. With a median follow-up of 7 months (range, 2–24) TRM at 100 and 180 days was 14% and 20% respectively, and was significantly increased in patients 〉 30 yrs (25% vs 14%; p = 0.05) and in those with a previous ASCT (51% vs 13%; p 〈 0.01). Causes of death (22 pts) were infection (11; 3 aspergillosis, 2 bacterial blood stream infections, 2 tuberculosis, 2 pneumonia, 1 CMV disease and 1 toxoplasmosis), relapse (5), GVHD (1), graft failure (1), veno-occlusive disease (1), post-transplant lymphoproliferative disorder (1), microangiopathic hemolytic anemia (1), and multiorgan failure (1).These results suggest that the present myeloablative conditioning regimen for single-unit UCBT offers a high and fast engraftment rate and a low incidence of both acute GVHD and TRM in patients with hematologic malignancies. Longer follow-up is required to assess its impact on relapse risk and DFS.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.618.618

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 665-667

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-160000

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7