Kooperativer Bibliotheksverbund

In: European Journal of Haematology, Wiley, Vol. 109, No. 3 ( 2022-09), p. 250-256

Abstract: High‐dose chemotherapy followed by autologous stem cell transplantation (auto‐SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto‐SCT in elderly patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto‐SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto‐SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto‐SCT. The median progression free survival (PFS) for graft versus no‐graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto‐SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.v109.3

DOI: 10.1111/ejh.13804

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2027114-1

In: Hematological Oncology, Wiley, Vol. 40, No. 1 ( 2022-02), p. 32-40

Abstract: The standard management for relapsed or refractory classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous stem cell transplantation (ASCT). This strategy allows almost 50% of patients to be cured. Post‐ASCT maintenance treatment with brentuximab vedotin (BV) confers improved progression‐free survival (PFS) to cHL patients at high risk of relapse. We investigated the outcome of 105 cHL patients receiving post‐ASCT BV maintenance in the real‐life setting of 23 Italian hematology centers. This population included naïve patients and those previously exposed to BV. Median follow‐up was 20 months. Patients presented a median of two lines of treatment pre‐ASCT, with 51% receiving BV. Twenty‐nine percent of patients had at least two high‐risk factors (refractory disease, complete response [CR] less than 12 months, extranodal disease at relapse), while 16% presented none. At PET‐CT, a Deauville score (DS) of 1–3 was reported in 75% and 78% of pre‐ and post‐ASCT evaluations, respectively. Grade 3–4 adverse events (AEs), mainly peripheral neuropathy, were observed in 16% of patients. Three‐year PFS and overall survival (OS) were 62% and 86%, respectively. According to BV exposure, 3‐year PFS and OS were 54% and 71%, respectively, for naïve and 77% and 96%, respectively, for previously exposed patients. Refractory disease (hazard ratio [HR] 4.46; p  = 0.003) and post‐ASCT DS 4–5 (HR 3.14; p  = 0.005) were the only two factors significantly associated with PFS reduction in multivariable analysis. Post‐ASCT BV maintenance is an effective, safe treatment option for cHL naïve patients and those previously exposed to BV.

Type of Medium: Online Resource

ISSN: 0278-0232 , 1099-1069

URL: Issue

URL: Article

DOI: 10.1002/hon.v40.1

DOI: 10.1002/hon.2939

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2001443-0

In: Annals of Pathology and Laboratory Medicine, Marwah Infotech, Vol. 9, No. 12 ( 2022-12-31), p. C67-70

Abstract: A 55-year-old gentleman presented to our hospital with a single inguinal adenopathy, and no other clinical symptoms or signs. An excisional lymph node biopsy was performed. Pathologic evaluation demonstrated follicular center site which stained positive for CD20, CD10, Bcl-2, Bcl-6, and mantle zone cells which demonstrated Cyclin D1 (CCND1) positivity, partial SOX11 positivity and no expression of CD5, suggesting the diagnosis of composite lymphoma comprising follicular lymphoma (FL) with in situ mantle cell neoplasia (ISMCN), the latter previously referred as in situ mantle cell lymphoma (MCLIS). FL is known as indolent non-Hodgkin lymphoma; however, the clinical significance of a coexisting ISMCN continues to be elusive, and optimal management of these patients remains largely unknown. This paper reports a new case of this extremely uncommon condition and also discusses reviews of the literature including advances in molecular pathogenesis and lymphoma genomics with the aim to offer novel insights into this rare hematological malignancy.

Type of Medium: Online Resource

ISSN: 2349-6983 , 2394-6466

URL: Article

DOI: 10.21276/apalm.3219

Language: Unknown

Publisher: Marwah Infotech

Publication Date: 2022

In: Blood Advances, American Society of Hematology, Vol. 5, No. 21 ( 2021-11-09), p. 4370-4379

Abstract: The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36). The prevalence of late comorbidities and health problems was also assessed. The clinical significance of differences was evaluated based on predefined thresholds. A total of 161 of 232 potentially eligible patients were analyzed, of whom 83 were treated with ATRA-ATO and 78 were treated with ATRA chemotherapy. The median time since diagnosis of the study sample was 8 years. The 2 largest clinically meaningful differences in the EORTC QLQ-C30 were observed for role functioning (Δ = 8.4; 95% confidence interval [CI], 0.5 to 16.3) and dyspnea (Δ = −8.5; 95% CI, −16.4 to −0.7), favoring patients treated with ATRA-ATO. With regard to the SF-36 results, a clinically relevant better physical component score (Δ = 4.6; 95% CI, 1.3 to 7.8) was observed in patients treated with ATRA-ATO, but this was not the case for the mental component score. The 2 groups showed similar profiles in the scores of the EORTC QLQ-CIPN20 scales and in the prevalence of late comorbidities. Overall, our findings suggest that the greater and more sustained antileukemic efficacy of ATRA-ATO is also associated with better long-term patient-reported outcomes than ATRA chemotherapy. This study was registered at www.clinicaltrials.gov as #NCT03096496.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2021004649

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 2876449-3

In: Cancer, Wiley, Vol. 122, No. 9 ( 2016-05), p. 1461-1462

Type of Medium: Online Resource

ISSN: 0008-543X , 1097-0142

URL: Issue

URL: Article

DOI: 10.1002/cncr.v122.9

DOI: 10.1002/cncr.29943

Language: English

Publisher: Wiley

Publication Date: 2016

detail.hit.zdb_id: 1479932-7

detail.hit.zdb_id: 2599218-1

detail.hit.zdb_id: 2594979-2

detail.hit.zdb_id: 1429-1

In: Cancer, Wiley, Vol. 103, No. 3 ( 2005-02-01), p. 582-587

Type of Medium: Online Resource

ISSN: 0008-543X

URL: Issue

URL: Article

DOI: 10.1002/cncr.v103:3

DOI: 10.1002/cncr.20826

Language: English

Publisher: Wiley

Publication Date: 2005

detail.hit.zdb_id: 1479932-7

detail.hit.zdb_id: 1429-1

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5257-5257

Abstract: INTRODUCTION MCL is an incurable disease and treatment approach should be adapted to patient's characteristics: age, PS, co-morbidities, social conditions, presence of caregiver, etc. In this study we describe the experience of RELLI in real life about old MCL pts followed in Latium region and diagnosed and registered in our database between January 2013 to December 2017. MATHERIALS and METHODS Data were collected in a regional data base. All new diagnosis of lymphoproliferative disease were considered medical history, clinical characteristics and lymphoma related characteristics were registered starting from an existing data base or medical records of single Institutions. RESULTS In the database were registered 91 pts with MCL (70M/21F) older than 65 years with a median age of 74 yrs (range 66-87). At diagnosis 11/91 (12.1%) were in stage I-II and 80/91 (87.9%) in stage III-IV; only 6 (6.6%) pts presented systemic symptoms. High levels of LDH were present in 45.1% of pts, at least one extranodal localization was reported in 4.4% and Ki67 〉 30% in 48.5%. Prognostic score was evaluated at diagnosis: MIPI (LR 46.5%, IR 19.7%, HR 33.8%) and MIPI-c (LR 36.6%, ILR 22.5%, IHR 22.5%, HR 18.4%). Treatment was evaluated according to the age of pts: 65 -70 and 〉 70 years; in the first group immuno-chemotherapy (ICT) was: Benda containing regimen 43.5% (R-BAC 17.4%, R-B 26.1%) and CHOP-like regimen 36.1% (R-CHOP21 17.4%, R-COMP21 8.7%). In contrast in older pts the choice of ICT was: Benda containing regimen 64% (R-BAC 14.8%, RB49.2%), and CHOP-like regimen 13.1% (R-CHOP21 8.2%, R-COMP 4.9%).The overall response rate (ORR), progression free-survival (PFS) and overall survival (OS) were calculated from the start of treatment and evaluated in the two groups of pts: ORR was 100% in younger (CR 69.6%, PR 30.4%) and 68.8% in older (CR 50.8%, PR 18%). According to the type of ICT, as expected, pts treated with bendamustine containing regimens (+/- Cytarabine) have better response and longer survival. With a median follow-up of 34.5 months, media OS of the entire population isn't reached and PFS is projected at 50% at 60 months. CONCLUSIONS In the era before new biologic drugs the approach to treatment of MCL was sufficiently homogeneous in the Lazio region. In real life Ky67 was principal factor influencing OS. MIPI and MIPI-c score divided the entire population into two groups at high and low risk. Age not change the OS but only the response rate to treatment (Figure 1). Disclosures Abruzzese: BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Di Rocco:Roche: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Sandoz: Consultancy. Martelli:F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Servier: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124696

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. 136, No. Supplement 1 ( 2020-11-5), p. 32-33

Abstract: Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with specific morphologic and molecular features and excellent prognosis. Although high rate of complete response (CR) has been reported after treatment with purine analogs, expecially cladribine (2CDA), relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long term remission rate and overall survival (OS) in those patients (pts) that received 2CDA as first line treatment. We retrospectively reviewed data of all HCL pts treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers. Among 553 pts reported, only 513 were evaluable because treated with 2CDA alone. Considering the clinical carachteristics, M/F ratio was 4.5 with a median age of 54 years (range 24-88) and ECOG 0 in 85% of cases. Splenomegaly and presence of circulating hairy cells recorded by morphology were reported in 241 (47%) and 138 (27%) pts, respectively. Thirty-seven (7%) pts presented with an infection. Other comorbidities were cardiovascular in 29 (6%) pts, a previous cancer or diabetes in 27 (5%) each, chronic hepatic disorders in 18 (3%), obstructive pulmonary disease in 16 (3%), chronic kidney disease in 3 (1%). Three hundred-thirty (64%) pts received 2CDA intravenously (253 as daily continuous infusion for 5-7 consecutive days and 77 as weekly infusion for 5-7 consecutive weeks) and 183 (36%) subcutaneously. Response criteria were defined as per recent consensus guidelines (Grever MR et al. Blood 2017). The overall response rate (ORR) was 83%: CR in 335 pts (65%) and partial response (PR) in 96 (19%); 40 (8%) pts obtained hematological improvement (HI) and in 42 (8%) no response was observed. Nine of 11 (82%) pts with HI and 18/25 (72%) non responders who received salvage therapy obtained a major response (fig. 1). A slightly higher hemoglobin value (12.4 vs 11.4 g/dl, p=0.044), a reduced frequency of circulating hairy cells (28.7% vs 31.8%, p=0.039), absence of palpable splenomegaly (p= & lt;0.001) and a faster recovery of ANC (28 days vs 41 days, p= 0.006) were associated with CR compared to PR in univariable analysis. No differences in terms of quality and duration of response, infection rate and time to blood counts recovery were reported according to the 2 routes of administration. Among pts receiving intravenous 2CDA, ORR was 85% for continuous infusion and 78% for weekly infusion: no statistically significant difference could be observed. Median duration of response was 12.2 years: 75.1%, 53.6% and 45.5% of responding pts are expected to be free from relapse at 5, 10 and 15 years, respectively. A statistically significant difference in duration of response was identified between pts that obtained a CR compared to pts in PR (19.4 years versus 4.7 years, p & lt;0.0001) (fig. 2). No other differences in relapse free survival (RFS) were identified. Non-hematological grade-3 or higher early toxicity was reported in 108 (21%) pts, due to infections in 102 cases (20%), mainly fever of unknown origin and pneumonia. In 6 cases infection due to invasive aspergillosis, bacteric pneumonia and bacteric sepsis caused the death of pts. Other non-hematological adverse events were almost all grade-1 allergy (47 pts, 9%). No late toxicity was reported, but 19 (4%) second cancers were observed. Among 118 pts relapsed after a median of 4.4 years (fig. 1), 85 (72%) were retreated with 2CDA, alone (65 cases) or associated with rituximab (20 cases); 11 (9%) with pentostatin, alone (7 cases) or associated with rituximab (4 cases), 8 (7%) with interferon α, 8 (7%) with rituximab alone, 1 (1%) with vemurafenib and zanubrutinib each; 2 were lost at follow-up and 2 died before retreatment. Overall, 58 (51%) retreated pts obtained a CR (42 after 2CDA), 37 (32%) a PR (32 after 2CDA), 7 (6%) a HI (4 after 2CDA) and 12 (11%) did not show any response (6 after 2CDA). Median OS was not reached; 95.7%, 92.8% and 82.3% of pts are expected to be alive at 5, 10 and 15 years, respectively (fig. 2). Overall 51 pts died (10%), during the induction phase in 6 cases and during follow-up in 45: overall, mortality was HCL-related in 14 patients (2 progression of disease and 12 infections) and HCL-unrelated in 37 patients (cardiovascular events in 16, natural causes in 15, a second cancer in 6). 2CDA is greatly effective in treating HCL, with an ORR of 83%. Early and long term adverse events were rare and easily managed: although HCL-related mortality is still possible, OS at 15 years is higher than 80% Disclosures Motta: Roche: Honoraria; Janssen: Honoraria. Offidani:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Tedeschi:Abbvie: Honoraria, Speakers Bureau; Sunesis: Honoraria, Speakers Bureau; Acerta: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Beigene: Honoraria, Speakers Bureau. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Varettoni:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Visentin:Janssen: Honoraria; Gilead: Honoraria; Abbvie: Honoraria. Falini:Roche: Research Funding. Pulsoni:Sandoz: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Gilead: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; roche: Consultancy, Speakers Bureau; Merk: Consultancy. Tiacci:Roche: Research Funding; Abbvie: Other: Travel and meeting expenses. Zinzani:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136633

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5451-5451

Abstract: High dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) is now considered standard therapy in patients (pts) with Multiple Myeloma (MM) aged less than 65–70 years. Using this therapeutic approach, newly diagnosed MM pts may achieve a complete remission rate of 30–50% associated to prolonged disease-free and overall survival (OS) rates. Unfortunately, HDT followed by ASCT is not curative and only a small fraction of pts remains free of disease after a long follow-up. In this study we analysed the different patterns of relapse after HDT and ASCT in 91 previously untreated MM pts (M/F : 46/45; median age: 54 years, range 32 – 69). As for stage, according to Durie and Salmon criteria, 4 pts (4%) were stage IA, 26 (29%) IIA, 57 (63%) IIIA and 4 (4%) were stage IIIB. The monoclonal component (MC) was: IgG in 54 pts (60%), IgA in 23 pts (25%), IgD in 2 pts (2%); 11 pts (12%) had a micromolecular MM (k/l were 8/3). Only one patient had a non-secretory MM. Median bone marrow plasma cells were 43%. Of the 91 pts, 5 were not evaluable for response because had died early during the transplantation procedure. Causes of death were: hepatic toxicity (1 patient), cardiac complications (1 patient) and hemorrhagic complications (3 pts). Of the remaining 86 evaluable pts, 84 (98%) achieved an objective response and 2 (2%) showed a progressive extramedullary disease (cutaneous and thoracic). After a median follow-up of 49 months (range 6–169) from the HDT-ASCT, 45/84 (54%) responding pts have relapsed and 38/84 (46%) are still alive and responding, the remaining patient was lost to follow-up and considered as event in both OS and event free survival (EFS) curves. The relapse type was “classical” (bone marrow + increase in MC) in 34 (75%) pts, extramedullary in 8 (18%) pts and of both type in 3 (7%) pts. Extramedullary relapse was defined by the presence of normal bone marrow, no increase in MC and presence of plasma cell tumour masses outside the bone marrow demonstrated by clinical examination, imaging and histology. As of July 31 2006, the median OS was not yet reached with 66% of pts still alive. The median overall EFS and time to progression (TTP) were: 82 and 89 months, respectively. As for the 34 pts with “classical” relapse and the 8 pts with extramedullary relapse, median OS and EFS were 120 and 29 months versus not reached and 85 months, respectively. The median time from HDT-ASCT to extramedullary relapse was 85 months. Sites of extramedullary relapse included vertebral and para-vertebral localization (7 pts), humeral localization (2 pts) and thoracic localization (1 patient); one patient presented humeral and pancreatic localization. The 8 pts with isolated extramedullary relapses were treated by local radiotherapy (4 pts), radiotherapy combined to Melphalan-Prednisone (MP) (3 pts) and a combination of surgical treatment + MP (1 patient). In conclusion, HDT-ASCT has greatly improved the prognosis of MM pts, however about 10%–15% of transplanted pts experience an extramedullary relapse probably due to sub-clinical seeding of tumor cells suggestive of the presence of an extramedullary clone of plasma cells with a high degree of chemo resistance responding, however, to radiotherapy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V108.11.5451.5451

Language: English

Publisher: American Society of Hematology

Publication Date: 2006

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2004-2004

Abstract: Background. Similar probabilities of survival have been reported for patients transplanted from Matched Unrelated Donor (MUD), Umbilical Cord Blood (UCB) or Haploidentical (Haplo) donors as alternative hematopoietic stem cell sources. However, few studies have compared these results with those obtained in patients transplanted from HLA Id-siblings (Id-sib). Moreover, all reported studies are retrospective and the criteria of donor selection were not predefined. We report the intention to treat (ITT) analysis results on 238 patients with high-risk acute myeloid leukemia (AML) prospectively transplanted according to the policy of the Rome Transplant Network (RTN), a metropolitan transplant program established in Rome in 2006. Patients and Methods. For AML patients eligible to an allogeneic transplant, the RTN policy consists of an algorithm of donor choice based on a hierarchy according to the following criteria: 1) HLA identical sibling; 2) MUD ≥8/10 HLA 3) UCB as single unit selected on the base of cell dose and number of HLA disparities (0-1/6 HLA: TNC ≥2.5x107/kg and CD34 ≥1x105/kg; 2/6 HLA: TNC ≥3.5x107/kg and CD34 ≥2x105/kg); 4) G-CSF primed, unmanipulated bone marrow Haplo donor. Myeloablative (MAC) or reduced intensity (RIC) TBF (Tiothepa, Busulfan, Fludarabine) conditioning regimen was identical for all patients, GVHD prophylaxis was uniform for each categories. of transplant Results. From January 2006 to December 2014, 238(89%) out of 303 adult patients candidates to an allogeneic transplant for high-risk AML were considered eligible. Overall, a donor was available for 205 (86%) of 238 eligible patients. At time of the analysis, 17 of these 205 patients (8%) had lost the transplant eligibility and 4 (2%) were still scheduled for transplant, therefore 184/205 (90%) patients with an available donor were finally transplanted from Id-sib (n=76), MUD (n=38), UCB (n=17) or Haplo (n=53) donors. The 8-yrs overall survival (OS) of the 238 eligible patients from time of HLA typing and of the 184 transplanted patients from time of the graft was 40±4%and 43±4%, respectively. By excluding the low number of UCB recipients (n=17), the OS was particularly dismal for the 34 patients transplanted in advanced disease phase (7±4% at 4 yrs), whereas for the 132 patients transplanted in early (CR1+ CR2) phase the 8-yr OS was 56±5%: 58±7% for 61 HLA Id-sib, 50±8% for 40 Haplo and 63±10% for 27 MUD recipients (P=NS). The OS of patients transplanted in early phase was 63±5% for 97 patients receiving MAC and 33±9% for RIC recipients. For these 97 patients, the survival by type of donor was 62±10% either for 47 Id-sib or 28 Haplo and 70±10% for 22 MUD recipients (P=NS). The results were analyzed by various donor/recipient (D/R) combinations such as age, sex and CMV status. The median donor age was 39 years (range, 18-70) and the median patient age was 43 years (range, 16-59): the 8-yr OS of patients (n=30) with younger D/R combination (D 〈 39y-R 〈 43y) was79±9%, significantly higher than 55±7% observed for the other D/R combinations (P=0.04). The 4 D/R sex combinations were homogeneously distributed among Id-sib, MUD and Haplo recipients: for 51 sex mismatched (DM/RF; DF/RM) patients the 8-yr OS was 73±7%, significantly higher than the 53±8% rate observed for 46 sex matched patients (P=0.03). Finally, the 8-yr OS by D/R CMV status was 68±6% for 74 D/R CMV matched and 46±12% for D/R CMV mismatched patients (P=NS). In multivariate analysis, the factors influencing survival were D/R age (P=0.059), D/R sex (P=0.03) and D/R CMV status (P=0.04). The donor source (Id-sib vs MUD vs Haplo) did not affect survival (P=NS). Conclusions. RTN policy allowed donor identification in 86% of all eligible AML patients and allowed an allogeneic transplant to be carried out in 90% of them with no substantial differences in terms of long-term survival between initially eligible (ITT analysis) and definitively transplanted patients. Only the definition of a specific transplant policy and the ITT analysis allow to evaluate the real impact of a transplant program. As the probability of survival is not substantially different comparing different donor stem cell sources, the final conclusion which can be drawn from our study is that for patients with AML undergoing an allogeneic transplant, the HLA matching is unlikely to remain the first criterion for donor identification. Other factors such as D/R age, sex and CMV status should drive the search for the best donor. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2004.2004

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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detail.hit.zdb_id: 80069-7