FB, FE and SS contributed equally to the work.
Background. The best post-remission treatment for younger acute myeloid leukemia (AML) patients remains controversial (Cornelissen JJ & Blaise D, Blood ...2016, 127, 62-70). Most prospective studies comparing autologous (auto-) to allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) have been published with a relatively short follow-up.
Aim. The main objective of this study was to provide a long-term follow-up evaluation of patients previously enrolled in the EORTC/GIMEMA AML-10 study.
Methods. In the EORTC/GIMEMA AML-10 prospective trial, 2157 patients aged 15-60 years were randomized to receive either daunorubicin (DNR) (50 mg/m2/d), mitoxantrone (MXR) (12 mg/m2/d), or idarubicin (IDA) (10 mg/m2/d) on days 1, 3 and 5 in addition to standard-dose cytarabine and etoposide for induction chemotherapy. A second cycle of induction was administered in patients who achieved a partial response while patients who achieved a CR or a CR with incomplete counts recovery (CRi) after 1 or 2 courses of induction chemotherapy received consolidation chemotherapy with the same anthracycline as in the induction course plus intermediate dose cytarabine. Young (≤ 45 years old) patients were then scheduled to receive an allo-HCT in first CR/CRi if they had an HLA-identical sibling donor or an auto-HCT otherwise. Median follow-up at the time of the initial report was 5.6 years (Mandelli et al., J Clin Oncol 2009, 27, 5397-5403). For the current analyses, cytogenetics were centrally reviewed and re-classified using the UK Medical Research Council (MRC) classification.
Results. In the current report, median follow-up was 11 (95% CI, 9-15) years. The 5-, 10-, 15- and 20-year overall survival (OS) rates were 33.2%, 30.1%, 28.0% and 26.1% respectively. No significant difference between the 3 randomized groups regarding OS was observed (Table 1). In young patients, the OS was comparable in the 3 treatment groups, whereas, in older patients, who had generally a worse outcome, OS was prolonged in the MXT and IDA groups as compared to the DNR group (Table 1). As expected, the initial MRC cytogenetic risk group had an important impact on OS. Within each subgroup, treatment outcomes were quite homogeneous (Table 1).
The impact of auto- versus allo-HCT was assessed in a cohort of 839 patients ≤ 45 years old who achieved a CR/CRi after induction chemotherapy, who generally received consolidation chemotherapy, and who were HLA-typed. A total of 330 patients had an HLA-identical sibling (donor group) while the remaining 509 patients had not (Table 2). The 10- and 15-year DFS and OS rates from CR were approximately 10% higher in patients with a donor as compared to those without (Table 2). Assessing the impact of donor availability on the DFS according to cytogenetic risk group, we observed that patients with a donor had a higher 10- and 15- yr DFS rates in all but those in the favorable MRC cytogenetic subgroup (table 2).
Among patients aged 46-60 years, 635 reached CR/CRi. The outcomes (DFS and OS) of CR/CRi patients with a donor were only marginally prolonged as compared to those without a donor, which can be explained by the positive effect of decreased relapse rate being neutralized by an increased risk of death in CR/CRi. The 10- and 15-yr DFS rates were increased by 6-11% in the MXR and IDA groups as compared to the DNR (overall logrank P=0.12); the HR (MXR vs DNR) was 0.88 (99% CI, 0.66-1.17), and the HR (IDA vs DNR) was 0.79 (99% CI, 0.58-1.06). The 10- and 15-yr OS rates were also increased, by 7-14% in the MXR and IDA groups as compared to the DNR (overall logrank P=0.04); the HR (MXR vs DNR) was 0.86 (99% CI, 0.64-1.16) and the HR (IDA vs DNR) was 0.74 (99% CI, 0.54-1.10).
Conclusions. Long-term follow-up of the EORTC/GIMEMA AML-10 trial confirmed that, overall, similar outcomes were obtained by using either DNR, MXR or IDA. In young patients without favorable cytogenetic features, who reached CR/CRi, the long-term outcome of those with a HLA-identical donor, who generally received AlloHSCT, was improved as compared to those without a donor. In older patients who reached CR/CRi, allo-HSCT and auto-HSCT yielded similar outcomes; however, MXR and IDA administered during induction and consolidation, provided better results than DNR.
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Efficace:Incyte: Consultancy; Lundbeck: Research Funding; TEVA: Consultancy, Research Funding; Seattle Genetics: Consultancy; Amgen: Consultancy, Research Funding. Guimaraes:Janssen: Speakers Bureau; Pfizer: Honoraria; Servier: Honoraria; Roche: Honoraria; Incyte: Speakers Bureau.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The DIPSS was not predictive of survival in myelofibrosis secondary to essential thrombocythemia or polycythemia vera after stem cell transplantation.•The MYSEC-PM predicted survival and showed ...improved prognostic ability.•Although performance of the MYSEC-PM was still moderate, risk stratification may be improved by incorporating clinical, mutational, and transplant-related factors.
We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques, has been only recently introduced for ...treating anal cancer patients. We report efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer. Materials and methods We retrospectively analyzed efficacy and toxicity of HT with or without chemotherapy for anal cancer patients. Local control (LC) and grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported. Results Between October 2007 and May 2014, 78 patients were treated. Fifty patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3 disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8 Gy/fraction) delivered to the anal and to nodal gross tumor volumes. Concomitant chemotherapy was delivered in 73 patients, mainly using mitomycin C and 5-fluorouracil (n = 30) or mitomycin C and capecitabine combination (n = 37). After a median follow-up period of 47 months (range 3-75), the five-year LC rate was 83.8% (95% CI 76.2-91.4%). Seven patients underwent a colostomy because of local recurrence (n = 5) or pretreatment dysfunction (n = 2). Overall incidence of grade 3 acute toxicity was 24%, mainly as erythema (n = 15/19) or diarrhea (n = 7/19). Two patients presented a late grade 3 gastrointestinal toxicity (anal incontinence). No grade 4 acute or late toxicity was recorded. Conclusions HT with daily IGRT is efficacious and safe in the treatment of anal canal cancer patients, and is considered in our department standard of care in this clinical setting.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objectives
The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), ...non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant.
Methods
A retrospective analysis of the EBMT database (1991‐2012) was performed.
Results
A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276).
Conclusion
From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Myeloid sarcoma (MS) is defined as a tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than bone marrow (BM). MS may occur before, concurrently ...or after a characterized acute myeloid leukemia (AML). Cytogenetic abnormalities are found in 50% of the cases but molecular alterations are less well described and involved FLT3 and/or NPM1 mutations. Mutations in IDH1 and IDH2 genes are found in 15% to 20% of patients with AML but have never been described in MS. Mutated IDH enzymes produce in vast excess D-2-hydroxyglutarate (2-HG) in leukemic cells, which can act as a biomarker predictive of the presence of IDH1 and IDH2 mutations. As availability of DNA sequencing techniques on paraffin samples are limited, molecular characterization of MS remained difficult. We asked whether in MS, serum 2-HG would predict the presence of IDH1/2 mutations at diagnosis, and could provide a biomarker for follow up.
Tissue samples and serum samples from 8 patients with a MS diagnosis were analyzed. High quality genomic DNA was extracted from frozen MS samples using conventional phenol/chloroforme extraction procedures. Exon 4 of IDH1 and IDH2 genes (IDH1/R132 and IDH2/R140 and /R172 codons) was amplified by PCR using HotStar Taq polymeraze (Qiagen) and primers. Direct sequencing was performed using the Sanger method as previously described. In case of MS relapse or AML evolution, IDH1 and IDH2 genes were analyzed in the same way from frozen tissue sample or bone marrow sample.
Serum samples at MS diagnosis were analyzed for total 2-HG, D-2-HG and L-2-HG by reverse-phase liquid chromatography coupled to mass spectrometry. In case of myeloid sarcoma with IDH1/2 mutation, 2-HG values were compared to 18F-FDG-PET results when available during remission phase and at relapse.
Three patients (3/8; 37.5%) had an IDH2 R140Q mutation at diagnosis of MS localized to lymph node, soft tissue, skin or pharynx. At MS diagnosis, serum total 2-HG, D-2-HG and ratio D/L-2-HG were significantly higher in case of myeloid sarcoma with IDH2 R140Q mutation compared to patients with no IDH mutation (Table 1). Serum total 2-HG level ≥2µM or D-2-HG level ≥1.8µM or ratio D/L 2-HG >2.5 were significantly associated with the presence of IDH2 mutation (Fisher's exact test P≤0.02).
Table 1Myeloid sarcoma with IDH2 R140Q mutation (N=3)Myeloid sarcoma without IDH2 R140Q mutation (N=5)Median total 2-HG (µM)4.1 (range: 3.1-30.1)1.4 (range: 1-1.6)Median D-2-HG (µM)3.7 (range: 2.3-28)0.6 (range: 0.5-0.8)Median L-2-HG (µM)0.8 (range: 0.4-2.1)0.8 (range: 0.4-0.8)Median ratio D/L 2-HG8.3 (range: 2.9-18.8)1 (range: 0.7-1.7)
All 3 patients with IDH2 R140Q mutated MS received intensive chemotherapy treatment and achieved complete remission (CR). Two patients relapsed: one experienced isolated extramedullary relapse (thigh muscle); one had a bone marrow relapse. IDH2 R140Q mutation was found at the site of relapse in both cases.
When available, serum 2-HG values and 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) were compared at different time points (at diagnosis, remission and relapse; Table 2).
Table 2Patient #1Patient #2Patient #3FDG-PET at diagnosis (SUVmax)-175.25Serum 2-HG at diagnosis (µM)4.13.130.1FDG-PET in remission (SUVmax)0 - 9.6 (N=4)0 (N=4)-Serum 2-HG in remission (µM)0.5 - 1.1 (N=4)0.6 - 3.1 (N=4)3.4 - 17.9 (N=3)FDG-PET at MS relapse/evolution to AML (SUVmax)6.1-0Serum 2-HG at MS relapse/evolution to AML (µM)2.3-16.7Time between diagnosis and MS relapse/evolution to AML (months)30-9
Serum 2-HG values were in accordance with FDG-PET interpretations except in patient #1 who presented a transient hypermetabolic splenic nodule (SUVmax 9.6) without serum 2-HG increase. Patient #2 remained in CR but had recently increased 2-HG values without overt relapse. Patient #3 presented relapse as a refractory anemia with excess of blast without extra-medullary localization. FDG-PET didn't find any abnormality contrary to the persistent increased value of serum 2-HG (total 2-HG: 16.7µM).
These data show that myeloid sarcoma can be associated with IDH2 R140Q mutation and suggest that 2-HG measurement in the serum predicts the presence of IDH1/2 mutations at diagnosis. During follow-up, serum 2-HG values could be representative of the disease status. Because of IDH inhibitors promising results in AML, 2-HG screening at MS diagnosis could be useful.
Ribrag:Celgene: Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmamar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. De Botton:Agios pharmaceuticals: Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but ...it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Background: Locally advanced HNSCC is treated curatively, but recurrence is common. In HNSCC, EGFR is richly expressed and EGFR inhibition is validated treatment (tx); the ErbB ...family blocker afatinib (A) showed efficacy in recurrent/metastatic disease. This Phase III trial assessed if A after definitive CRT improves disease-free survival (DFS). Methods: Eligible pts had complete response after CRT ≥66 Gy (or equivalent) with concurrent cisplatin or carboplatin but not prior EGFR inhibition, for HNSCC of oral cavity, hypopharynx, larynx, or oropharynx with >10 pack years (pk yrs) tobacco use. Pts were stratified by ECOG PS (0/1) and nodal stage (N0–2a/N2b–3), and randomized 2:1 to A 40 mg/d or placebo (P); tx continued for 18 m if tolerated, or until disease recurrence. The primary endpoint was DFS. Results: Of 669 pts planned, 617 were randomized; A 411, P 206. Median age was 58 yrs; 86% were male; 65% ECOG PS 0; most had smoked (A/P ex-smoker: 66/72%; current: 28/22%). Subsites (A/P) were: oropharynx 53/54%; hypopharynx 21/23%; larynx 18/12%; oral cavity 9/10%. The majority had T3 or 4 (A/P 70/68%) and N2 disease (67/63%). Accrual was halted for futility on independent DMC recommendation: at a pre-planned interim analysis (40% of DFS events), median DFS was A 43.4 m vs P not reached (NR; HR 1.13 95% CI 0.81–1.57, p=0.48); the Table shows key subgroups. Median treatment duration was A 300.0 d, P 455.5 d. Recurrence was A 23%, P 23%. Dose reduction of A was required in 53% (mostly due to diarrhea, stomatitis). Tx was discontinued due to AEs in A 15%, P 4%. Conclusions: A after CRT did not improve DFS vs P. Subgroup analyses were underpowered to provide definitive conclusions. Harrington and Cohen contributed equally. Clinical trial information: NCT01345669. Table: see text
Introduction: Hematopoietic stem cell transplantation (HSCT) is a major treatment for many hematological disorders. However, this treatment comes with significant risks linked to toxicity and ...infectious complications which may lead to death. Recently haploidentical transplants without ex vivo T-depletion have been developed through the use of post-transplant cyclophosphamide, thus reducing the risk of lethal GVHD. Toxicity data are still limited and few studies have evaluated infectious complications following haploidentical transplants without ex vivo T-cell depletion. In this study, we evaluated the incidence of infectious complications in patients who received haploidentical HSCT with post-transplant cyclophosphamide.
Patients and methods: Data from 21 French centers and one Belgian center were retrospectively collected. Between January 2013 and December 2014, 159 patients all older than 18 years, affected with hematological malignancy and having undergone a haploidentical HSCT were included. Informed consent was obtained in accordance with the Declaration of Helsinki. Clinical data were obtained through ProMISe (Project Manager Internet Server), the internet-based system shared by all Francophone transplantation centers. Results: In total, 159 patients were included (Table 1). The median age at transplantation was 51.2 years (20-72 years). All patients were treated with post-transplant cyclophosphamide combined with an anticalcineurin and mycophenolate mofetil as GVHD prophylaxis. The median follow-up of the cohort was 14 months. Meanwhile, 49 patients (13%) developed acute GVHD (grade 2-4). Forty-three patients (27%) developed chronic GVHD. Median overall survival wasn't reached and the median progression-free survival was 571 days. At the end of the study, 69 patients had died, 29 were in relapse and 36 presented treatment related toxicity. TRM was of 14% and 22% at day 100 and 365 respectively. At least one infectious complication occurred in 135 patients. These were mostly clinically or microbiologically documented. Median time from transplant to the first occurrence of infectious complication was 12 days. Twenty five percent of patients presented between 3 and 5 infectious complications. The average number of infectious complications per patient was 2.9 (0-12). Sixty-two percent of early infectious complications occurred throughout conditioning or within 20 days post- transplant. Fifty-two percent of those infections were bacterial, 33% viral (39% of which related to CMV and 28% to BK virus), and 4.5% were parasitic or fungal (50% of which related to aspergillosis). Overall 436 infectious episodes were reported: bloodstream infections (62%) (bacteremia, viremia, fungemia or parasitaemia), respiratory (10%), urinary tract (8%), digestive tract (6%), skin (3%), septic shock and multi organ failure (6%), others (5%). Among those complications, 46% were bacteria related, 36% were virus related (17% of which due to BK virus and 39% to CMV), 7% were parasitic or fungal related (in these cases, 61% aspergillosis related). In total, 26 cases (6%) of BK virus infections were observed. Conclusion: In conclusion, in these preliminary results, except for maybe in the case of BK infections, incidence of infectious disease after haploidentical HSCT seem not to differ to related or unrelated HSCT. Further prospective studies are necessary to confirm these results, especially by evaluating infectious viremia with BK virus after HSCT haploidentical with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning for this patient population. Table 1: Patient disease and treatment characteristics
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Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Many patients with relapsed or refractory Hodgkin's lymphoma (HL) undergo high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). However, most large reports ...include patients treated in the 90's. We aimed to analyze the outcome of a HL patients treated in the last decade with HDC and auto-SCT in a large cohort study.
Patients and methods
In the setting of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, we retrospectively analyzed 1987 consecutive adult patients (age < 65 years) with biopsy-proven HL who received a first auto-SCT between 2003 and 2014.
Results
Median age at auto-SCT was 33.7 years (range, 18-65) and 60% patients were male. Disease status at transplant was complete remission in 1040 patients (52%), partial response in 727 (37%) and progressive disease in 220 (11%). The main conditioning regimen was BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=1497). At one month, cumulative incidence of neutrophil engraftment was 97.6% (95% CI 96.8-98.2), whereas cumulative incidence of death without engraftment was 0.2% (95% CI 0.07-0.5). After a median follow-up of 16.4 months (IQR, 4.4-47.2), 3-year overall survival (OS), disease-free survival (DFS), cumulative incidences of relapse (IR) and non-relapse mortality (NRM) were 80.4% (95% CI 78.1-82.9), 59% (95% CI 56.1-62), 35.9% (95% CI 33.1-38.7) and 5% (95% CI 3.9-6.4), respectively. There was no significant difference in terms of outcome between patients treated during the time period 2003-2008 and 2009-2014. 3-year OS and DFS were 70.5% and 43.7% in patients with progressive disease at transplant, 75% and 52.1% in patients in partial response, 87.2% and 67.8% in patients in complete remission (p<0.0001 and p<0.0001, respectively). Male had a decreased 3-year OS compared to female (HR 1.46, 95% CI: 1.15-1.84; p=0.002). Age ≥ 35 years was associated with a higher NRM (HR 1.67, 95% CI: 1.06-2.65; p=0.029) but a better PFS (HR 0.77, 95% CI: 0.65-0.91; p=0.002). Overall, patient age did not significantly influence OS (p=0.19). Primary refractory or multiple relapsed patients had a worse outcome than the others. A number of previous treatment lines ≥ 3 negatively influenced OS (HR 1.91, 95% CI: 1.42-2.58; p<0.0001), PFS (HR 2.03, 95% CI: 1.60-2.56; p<0.0001), IR (HR 1.90, 95% CI: 1.48-2.45; p<0.0001) and NRM (HR 3.17, 95% CI: 1.69-5.96; p=0.0003). Cumulative incidence of NRM reached 9% at 3 years in these patients. Finally, patients who relapsed after auto-SCT (n=494) had a 3-year OS of 52.8% (95% CI 47.7-58.3).
Conclusion
In conclusion, HDC followed by auto-SCT is highly efficient in relapsed HL patients. However, relapse occurs in over 40% of patients < 35 years old or with partial response at transplant and in over 50% of patients with progressive disease at transplant or ≥ 3 previous treatment lines. Additional data are being collected to better identify which high-risk patients could benefit from post-transplant immunotherapy or tandem auto-allo transplant.
Brice:Roche: Honoraria; Bristol Myers-Squibb: Honoraria; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Seattle Genetics: Research Funding; Gilead: Honoraria. Salles:Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria. Peffault De Latour:PFIZER: Consultancy, Honoraria, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; ALEXION: Consultancy, Honoraria, Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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