Achievement a Negative 18-FDG/PET Status at the End of Procedure by Tailored Treatment According Pre-Transplantation Pet Status in Lymphomas Improve 5 Years-OS and EFS.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2193-2193
Author(s):  
Dominique Bordessoule ◽  
Benoit Marin ◽  
Stéphane Girault ◽  
Fredericka Bompart ◽  
Julie Abraham ◽  
...  

Abstract In patients (pts) with non Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) with poor prognosis factors, pre-transplantation (ASCT) 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) status is important for evaluation of response and predicting the outcome. A positive pre-ASCT PET (+PET) indicated a high risk (HR) of relapse which was increased by a positive post-ASCT PET. For these patients additional therapy (salvage therapies prior ASCT, targeted radiotherapy, second transplant or new treatment approaches) will be required (Spaepen K 2001, Filmont JE 2003; Svoboda J 2006, Mounier, 2007). In a french regional network, we try to obtain a negative metabolic status with additive « targeted-therapy », before or after the ASCT, in the hope to improve the clinical outcome for these HR NHL/HD. Objective: The study assessed the impact of tailored therapy according to pre-transplantation FDG-PET status on pts outcome after high-dose chemotherapy and ASCT. Patients & Methods: We performed a retrospective analysis of pts included according three criteria: 1) histologically proven malignant lymphoma (NHL/HD) with a metabolic active disease in PET imaging 2) planned to receive an ASCT for HR factors according international recommendations (de novo initial aaIPI III/IV or not in CR after front line chemotherapy or in early and unfavorable relapse; 3) having a PET prospectively performed prior and after ASCT on a CDET replaced in 2005 by a PET/CT (Siemens). The metabolic imaging interpretation had been performed by 2 experienced nuclear physicans first blinded to clinical and CT scan then discussed in multidisciplinary team. + PET defined as any focal or diffuse area of increased activity in a location suspect for residual disease and -PET if any metabolic activity according revised Cheson criteria. Survival analysis were performed using Kaplan-Meier method for event free survival (EFS), overall survival (OS). Results: For 95 consecutive pts treated from 05/1999 to 12/2006 18 HD and 77 NHL, an ASCT has been planned either in initial HR prognostic score (n=39), primary refractory disease (n=31), or in relapse (n=25). First line therapy were mainly ABVD for HD and ACVBP/CHOP +/− Rituximab for NHL. A pre-ASCT -PET was obtained in 52 pts (55%) and 43 pts (45%) remained pre-ASCT +PET. Additional salvage chemotherapy (MINE or DHAP(+/−R) most frequently) obtained a - PET status from pre-ASCT +PET in 9/43 pts (21%) prior the ASCT. ASCT has been performed for all these HR pts with a conditioning regimen mainly BICNU-Etoposide-Aracytine-Melphalan (BEAM). After ASCT, 22/43 pre-ASCT +PET pts were converted in a post-ASCT -PET status. Residual disease of post-ASCT +PET pts was treated by targeted radiation (n=11) or by a second transplant (n=2). One pre-ASCT -PET converted to positive (1/52). At the end of procedure, we obtained a –PET status in 88 pts (92%), persistant + PET in 7 pts (7%) (3 PR/4 PD). With a median follow-up of 4.14 years (range 0.61–9.48) since diagnosis, 15/43pts (35%) pre-ASCT +PET and 14/52pts (26%) pre-HDT/ASCT -PET pts relapsed. Mortality was 23% (22/95pts range -PET : 11/52 (21%) and +/−PET 11/43 (25%) respectively and 4/7 (57%) resistant +/+PET). In –PET and in +/−PET median OS and EFS were not reached, 5yOS was 79% and 73% (p=0.7) and 5 y-EFS 62% and 54% respectively (p=0.2). In residual post-ASCT+PET, median OS was 4,5 months. Conclusion: PET-guided consolidative therapy prior or post ASCT in patients with HR lymphoma is routinely feasible and could obtain a negative status in 92% of pts at the end of procedure and reduce relapses with encouraging results in terms of OS and EFS with a 5-y median follow-up. Next step is now on-going: including pts in multicentric PETdesigned trials to confirm prospectively the crucial role of the metabolic imaging to determine which is the best tailoring therapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3813-3813
Author(s):  
Sabine Tricot ◽  
Christine Decanter ◽  
Julia Salleron ◽  
Louis Terriou ◽  
Daniela Robu ◽  
...  

Abstract Abstract 3813 Background. Chemotherapy-induced ovarian failure is one of the most challenging side effects for female patients with lymphoma. For a given patient, it remains difficult to predict if ovarian failure will recover or lead to sterility. Anti-Müllerian Hormone (AMH) reflects primordial follicle depletion and may predict ovarian function recovery. In this study, we prospectively assessed AMH levels during and after treatment of young female patients with lymphoma. Methods. Patients diagnosed with any type of lymphoma and aged below 36 years were eligible. AMH level was measured before chemotherapy, 2 weeks after initiating chemotherapy, 2 weeks before last chemotherapy and every 3 months during 2 years. Median AMH levels at each time point were compared according to the type of chemotherapy regimen (ABVD versus alkylating containing regimen -excluding Dacarbazine-). Results. From April 2004 to May 2010, 100 patients from 7 centers were enrolled of whom 80 are currently evaluable. Diagnosis was Hodgkin lymphoma (n= 65) or non-Hodgkin lymphoma (n=15). Median age was 25 years old (range: 17–36). Forty-eight patients (60.8%) had extended disease and 32 (62%) had at least one risk factor according to validated prognostic score. Chemotherapy regimen consisted of: ABVD (n=51), BEACOPP (n=5), CHOP or CHOP-like (n=11), CHOP followed by BEAM high dose therapy and autologous stem cell transplantation (ASCT) (n=3), or various salvage (MINE or IGEV) followed by BEAM and ASCT (n=10). The median follow up after chemotherapy was 18 months (range 3 – 24 months). The median number of cycles of ABVD was 6 (range: 2–8) whereas for the other regimen, the median cumulative dose of alkylating agents was: cyclophosphamide, 4.5 g/m2; procarbazine, 5.6 g/m2; ifosfamide, 15 g/m2 and melphalan, 140 mg/m2. Baseline AMH was 15 pMol/L (range 4–73). As soon as 2 weeks after chemotherapy, all chemotherapy regimen induced a significant decrease of AMH levels: 5 pMol/L(range 3–45). AMH recovery was significantly different for patients treated with or without alkylating agents (p=0.01) at 6 months (3 v 13 pMol/L) and 12 months (3 v 19 pMol/L) after last chemotherapy. Moreover, at 2 years, patients treated with BEACOPP had persistently low AMH levels (≤3 pMol/L) whereas patients treated with CHOP or CHOP like regimen showed an increasing of AMH levels to 6 (3-34) pMol/L at 1 year after chemotherapy. Patients who underwent ASCT had lower AMH levels than patients treated by alkylating agents without ASCT, yet non significant at 1 year (p=0.09). Three pregnancies were reported 7, 16 and 24 months after last chemotherapy (two patients treated with ABVD and one with CHOP). Conclusion. Sequential AMH profiles during and after chemotherapy were divers. Different AMH profiles were observed for ABVD compared to alkylating-based regimen and also among alkylating-based regimen. AMH recovery started at 6 months after ABVD, at 1 year after CHOP regimen and later for other regimen. Longer clinical follow-up will confirm if no or delayed AMH recovery recovery always reflects severe ovarian failure and will help guiding our decisions of ovarian cryopreservation in the future according to the planned chemotherapy regimen. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1558-1558 ◽  
Author(s):  
Basciano A. Basciano ◽  
Craig Moskowitz ◽  
Andrew D. Zelenetz

Abstract Abstract 1558 Poster Board I-581 Purpose To determine the role of asymptomatic post-remission surveillance imaging in the diagnosis of first relapse and its impact on outcomes in patients with Hodgkin lymphoma (HL). Patients and Methods The impact of surveillance imaging on diagnosis of first relapse and outcomes was determined by analysis of a defined patient population with relapsed HL who underwent high dose therapy followed by autologous stem cell rescue (HDT/ASCR). We retrospectively identified 114 patients from the HDT/ASCR database with biopsy-confirmed, relapsed HL; 94 patients had adequate data and follow-up for inclusion in the analysis. Details of surveillance imaging were obtained including: frequency; type; indication; and results of post-remission imaging. The indication for imaging was classified as asymptomatic surveillance (AS) or clinically indicated (CI; i.e. to investigate symptoms or physical examination findings). We have previously reported a validated prognostic model for relapsed HL that found time from initial therapy, presence of B symptoms at relapse and extra-nodal disease at relapse to be adverse factors (Moskowitz et al. Blood 97:616). We determined the prognostic risk group (PRG) (low [L] 0-1 factor, intermediate [I] 2 factors, high risk [H] 3 factors) for all patients. Overall and failure-free survivals were determined using the methods of Kaplan and Meier. Results Patient characteristics included: median age 32 years; PRG L: 65%, I: 31%, H: 4%; AS 36 (38%), CI 58 (62%). The median follow-up for surviving patients was 7.4 years. The PRG (L, I/H) correlated to outcome, validating its applicability in this patient cohort: FFS at 5 years was 64.8% and 49.4% respectively, p=0.045. PRGs were evenly distributed between the AS and CI groups: L: 64% v 66%; I/H: 36% v 37% p=0.48. The FFS at 5 years for patients in the AS and CI groups was 58.4% and 59.3% respectively, p=0.9; similar there was no difference in 5 year OS, AS 62.4% and CI 73.3% p=0.6. Within a given risk group (L or I/H) patients in the AS group did not have a superior outcome compared to the CI group. Conclusion AS does not identify a group of patients with first relapse of HL with a more favorable risk profile according the MSKCC prognostic model. While nearly 40% of patients were identified with relapse as a consequence of AS imaging, this did not identify a group of patients with relapsed HL with improved outcomes compared to patients who had CI imaging. If these results are confirmed in a prospective study, AS may be safely eliminated in HL after remission to reduce cost and long-term risk of the diagnostic imaging. Disclosures No relevant conflicts of interest to declare.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8068-8068
Author(s):  
T. Iyengar ◽  
M. Hayashi ◽  
C. Leopold ◽  
B. J. Smith ◽  
R. Gingrich ◽  
...  

8068 Background: High dose chemotherapy followed by ASCT has been established as the therapy for refractory and relapsed HD. Relapse remains the primary contributor to an unsuccessful outcome after ASCT. Intensification of the conditioning regimen is one means of decreasing relapse and improving results. We report our experience with an augmented preparative regimen in patients (pts) with relapsed or refractory HD undergoing ASCT. Methods: Retrospective analysis of 89 consecutive pts from October 1984 to October 2004. All pts received high-dose chemotherapy with BCNU 600mg/m2 IV day -8, Etoposide 400mg/m2/day days -7, -6, -5, and -4, Ara-C 3gm/m2 IV every 12 hours for 8 doses starting day -7, and Cyclophosphamide 90mg/kg IV on day-2 followed by bone marrow (40 pts), peripheral blood (43 pts) or both (6 pts) rescue. Ten pts received planned XRT post-transplant. Survival data were estimated using Kaplan-Meier curves. Cox proportional hazards regression was used to assess the impact of variables on disease-free survival (DFS) and overall survival (OS). Results: A total of 89 pts were identified. Median age was 31 (range 16–62); 51 pts (57.3%) had received one prior therapy at the time of transplant. At transplant only 28 pts (34.6%) were in CR; 79.8% had sensitive disease (CR plus PR).Time to transplant was < 1 year for 17% of pts. With a median follow-up of 811 days, the 5 and 10-year DFS rates were 63.3% and 60.4%, respectively. The estimated 5 and 10- year OS rates were 47.3% and 33.7%. The rate of secondary malignancies at 10 years was 7.8%. Lack of B symptoms and stage at transplant were associated with improved DFS (p= 0.01 and p= 0.0005, respectively) and OS (p=0.002 and p=0.02, respectively). Patients with primary induction failure and resistant relapse did as well as patients with sensitive disease. Conclusions: Though ASCT has been beneficial in prolonging DFS and OS in pts with chemosensitive HD, there has been conflicting data regarding refractory disease. We propose that an intensified regimen, i.e. BVAC, may be of benefit in that setting. Only a large randomized trial can determine whether intensification of the preparative regimen can improve OS for such a population. No significant financial relationships to disclose.


2015 ◽  
Vol 135 (3) ◽  
pp. 156-161 ◽  
Author(s):  
Meirav Kedmi ◽  
Arie Apel ◽  
Tima Davidson ◽  
Itai Levi ◽  
Eldad J. Dann ◽  
...  

The escalated BEACOPP (escBEACOPP) regimen improves the outcome of patients with advanced-stage Hodgkin lymphoma (HL) but is associated with cumbersome toxicity. We analyzed the survival outcome of high-risk, advanced-stage HL patients treated with response-adapted therapy. escBEACOPP was administered for 2 cycles, and after complete remission (CR) or partial remission (PR) was observed on FDG-PET/CT, treatment was de-escalated to 4 cycles of ABVD. Sixty-nine patients were evaluated, of them 45 participated in the multicenter, phase II prospective study between 2001 and 2007. Sixty patients had an international prognostic score ≥3. At a median follow-up of 5.6 years, 4 patients had died, 2 of them due to advanced HL. After the initial 2 cycles of escBEACOPP, 52 (75%) patients were in CR and 17 (25%) had a PR. Progression-free survival and overall survival (OS) were 79 and 93%, respectively. OS was predicted from the results of early-interim FDG-PET/CT: 98% of the patients in CR and 79% of those with a PR (p = 0.015). Hematological toxicity was more frequent during the first 2 cycles of escBEACOPP than in the ABVD phase. In conclusion, this retrospective analysis indicates that combined escBEACOPP-ABVD therapy is well tolerated and efficacious in HL patients who achieve negative early-interim PET results, while a positive PET result partially identified those with a worse prognosis.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 764-764 ◽  
Author(s):  
Andreas Engert ◽  
Carsten Kobe ◽  
Jana Markova ◽  
Heinz Haverkamp ◽  
Peter Borchmann ◽  
...  

Abstract Abstract 764 Introduction The role of additional radiotherapy after chemotherapy for advanced-stage Hodgkin lymphoma is unclear. The German Hodgkin Study Group (GHSG) thus performed the HD15 trial in which advanced-stage Hodgkin lymphoma patients having residual disease after 6–8 cycles of BEACOPP were evaluated by 18F-fluorodesoxyglucose positron emission tomography (PET) following chemotherapy. Methods Entry criteria for the PET question in HD15 were partial remission (PR) after the end of chemotherapy with at least one involved nodal site measuring more than 2.5 cm in diameter by computed tomography (CT). Exclusion criteria included diabetes, elevated blood sugar levels and skeletal involvement with risk of instability. Calculations were restricted to those cases with either progressive disease (PD) or relapse within 12 months after PET or at least 12 months of follow-up. A total of 2,137 patients with de novo HL were included in HD15 of whom 728 had a tumor bulk ≥ 2.5 cm after BEACOPP chemotherapy and were qualified for the PET question. An expert panel performed the assessment of response and PET. Only PET-positive patients were scheduled for radiotherapy of residual disease. The negative prognostic value (NPV) of PET was defined as the proportion of PET-negative patients without progression, relapse or radiotherapy despite being PET-negative within 12 months. Results The full analysis set included 728 patients of whom 699 had at least 12 months of follow-up. Median age was 30 years, 57% were males and 66% had NS histology. Of the 728 qualified patients with residual disease ≥ 2.5 cm after BEACOPP, 74.2% were PET-negative and 25.8% PET-positive. In the PET-negative group, a total of 28 patients relapsed or had radiotherapy despite being PET-negative (8 patients including 1 relapsing patient) resulting in a negative prognostic value of 94.6% (95% CI 92.7% to 96.6%). With a median follow-up of 38 months, the time-to-progression after PET at 3 years was 92.1% for PET-negative patients counting radiotherapy as failure and 86.1% for PET-positive patients (95%-CI for difference -11.9% to -0.1%). Overall, only 11% of patients had additional radiotherapy as compared to 71% after BEACOPPescalated in our prior HD9 trial. In addition, there was no difference in PFS or overall survival as compared to our earlier trials in advanced-stage HL. Discussion The NPV of PET of 0.95 suggests that indeed only patients with residual disease after chemotherapy who are PET-positive need additional radiotherapy. PET-negative patients at least after BEACOPP can be spared from additional radiotherapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3197-3197
Author(s):  
Massimo Martino ◽  
Messina Giuseppe ◽  
Roberta Fedele ◽  
Giuseppe Irrera ◽  
Console Giuseppe ◽  
...  

Abstract Background: High-dose melphalan (HDM) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Bendamustine (BENDA) has a proved activity in hematological malignancies including both first line and relapsed MM. Methods: We conducted a phase II trial, adding BENDA to HDM before second ASCT, in a tandem ASCT strategy, in 32 patients with "de-novo" MM. All patients received a bortezomib-based induction therapy. High-dose cyclophosphamide (CY) and G-CSF were used to mobilize stem cells. Four to 6 weeks after the administration of CY, patients received HDM (200 mg/mq), followed by ASCT. Three to 6 months after the first transplantation, patients received a second ASCT with BENDA (200 mg/m2) to HDM (140 mg/m2) as conditioning regimen (BM). Results: The median age was 56 years (range 40 to 66). Overall, there was no transplant related mortality. The incidence of neutropenic fever and mucositis (grade 1-2) was 46.9% and 81.2%, respectively. No mucositis grade 3-4 was observed. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response (CR) improved to 62.5%. Overall response rate was 90.6%. After a median follow-up of 18,2 months, 4 patients had progressed and 1 died. Median progression free survival (PFS) was not reached and actuarial 2-year PFS and OS was 78% and 90%, respectively. Conclusion: Bendamustine plus melphalan is feasible as conditioning regimen for second ASCT in MM and should be explored for efficacy in a phase III study. Longer follow-up is needed to evaluate conversion rate and survival. Disclosures No relevant conflicts of interest to declare.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.


Blood ◽  
2020 ◽  
Vol 135 (9) ◽  
pp. 680-688 ◽  
Author(s):  
Richard Dillon ◽  
Robert Hills ◽  
Sylvie Freeman ◽  
Nicola Potter ◽  
Jelena Jovanovic ◽  
...  

Abstract Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study. After a median follow-up of 4.9 years, patients with negative, low (&lt;200 copies per 105ABL in the peripheral blood and &lt;1000 copies in the bone marrow aspirate), and high levels of MRD had an estimated 2-year overall survival (2y-OS) of 83%, 63%, and 13%, respectively (P &lt; .0001). Focusing on patients with low-level MRD before alloSCT, those with FLT3 internal tandem duplications(ITDs) had significantly poorer outcome (hazard ratio [HR], 6.14; P = .01). Combining these variables was highly prognostic, dividing patients into 2 groups with 2y-OS of 17% and 82% (HR, 13.2; P &lt; .0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y-OS, 56% vs 96%; HR, 3.24; P = .0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P = .003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).


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