New clinical grading system for chronic GVHD predicts duration of systemic immunosuppressive treatment and GVHD-specific and overall survival

Abstract Abstract 531 Unrelated donor HSCT has been considered a therapy of last choice in SAA, because of poor overall survival reported prior to 1998 (32% @ 5-years). This is due in large measure to low resolution donor-recipient HLA typing and the selection of patients. Survival after unrelated donor BM HSCT for SAA has improved in recent years with survival rates of approximately 75% @ 5-years when the donor and recipient are matched at HLA-A, -B, -C and –DRB1. Furthermore, improvements in conditioning regimen may also have reduced the rate of graft rejection. In recent years PBPC instead of BM are increasingly used and PBPC grafts now account for 25% of unrelated donor HSCT for SAA. An earlier report from the CIBMTR and the EBMT identified higher chronic graft-versus-host disease (GVHD) incidence and mortality after transplantation of PBPC from HLA-matched siblings compared to BM in patients with SAA aged ≤20 years. GVHD rates are higher after unrelated adult donor HSCT regardless of graft type, but the effects of PBPC on survival in patients with SAA are not known. Two hundred and forty nine patients transplanted in 2000–2007 received either BM (n=186) or PBPC (n=63) from unrelated adult donors matched at HLA-A, -B, -C, -DRB1. Median follow up was 3 years. Compared with recipients of BM, PBPC recipients were older (median age: 19 vs. 35 years), transplanted in 2006–2007 (37% vs. 46%), more likely to be male (47% vs. 65%), receive non-TBI containing transplant conditioning (fludarabine + cyclophosphamide or busulfan or melphalan ± anti-thymocyte globulin; 34% vs. 55%) and tacrolimus-containing GVHD prophylaxis (29% vs. 57%). Among patients who received TBI-containing regimens, approximately 90% of BM and PB recipients received TBI 200 cGy. There were no differences in patient performance score at HSCT, immunosuppressive treatment prior to HSCT and interval from diagnosis to HSCT (median time to HSCT was 13 months in BM recipients and 11 months, in PBPC recipients). As shown after HLA-matched sibling transplantation, the cumulative incidence of neutrophil recovery (30.5 × 109/L at day-28) and platelet recovery (≥20 × 109/L) was similar in recipients of BM (92% and 83%, respectively) and PBPC (95% and 90%, respectively). The day-100 probability of grades 2–4 acute GVHD was higher after PBPC than after BM (51% vs. 33%, p=0.01). The 3-year probability of chronic GVHD was higher after PBPC than after BM, in patients older than 20 years at HCT (60% vs. 41%, p=0.001) but not in younger patients (23% vs. 26%, p=NS). In multivariate analysis, the risk of mortality was higher after PBPC than after BM (HR 1.79, p=0.02). Other factors that predicted mortality included poor performance score (HR 1.95, p=0.009) and non-TBI transplant conditioning regimens (HR 1.96, p=0.006). Although patient age (>20 vs. ≤20 years) was significantly associated with chronic GVHD there was no significant effect of age on mortality (HR 1.21, p=0.47). The 3-year probability of overall survival adjusted for performance score and transplant conditioning regimen was 76% for BM and 60% for PBPC recipients (p=0.02). These data suggest that: 1) outcomes after URD HSCT for SAA are now similar to outcomes observed in MRD HSCT, 2) BM is the preferred graft source when considering unrelated donor HCT in patients with SAA and 3) the data also support low dose TBI in the preparative regimen for transplant conditioning. Disclosures: No relevant conflicts of interest to declare.

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Evaluation of NIH-Defined Chronic Graft-Versus-Host-Disease in a Rapamycin-Based Haploidentical Stem Cell Transplantation: Analysis of 113 Consecutive Patients with High Risk Haematological Malignancies

Blood ◽

10.1182/blood.v120.21.4198.4198 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4198-4198

Author(s):

Maria Teresa Lupo-Stanghellini ◽

Alessandra Forcina ◽

Daniela Clerici ◽

Attilio Bondanza ◽

Andrea Assanelli ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Chronic Gvhd ◽

Immunosuppressive Treatment ◽

Overlap Syndrome ◽

Graft Versus Host ◽

Nih Consensus Criteria

Abstract Abstract 4198 Background and Methods. Chronic Graft-versus-Host-Disease (GvHD) remains a serious complication after allogeneic stem cell transplantation. In 2005 the National Institutes of Health (NIH) established new criteria for chronic GvHD based on retrospective data and expert recommendations. Here we are reporting the prospectively evaluation of the incidence of NIH-defined chronic GvHD and its prognostic impact in 113 consecutive patients who underwent unmanipulated peripheral blood graft from an HLA-haploidentical relative after a treosulfan based conditioning at our Institution. The peculiarity of this setting relies on the exploitation of a rapamycin-based, calcineurin-inhibitor-free regimen for prophylaxis of GvHD to induce in-vivo expansion of T-regulatory cells (Tregs). Results. Chronic GvHD was evaluable in 81 patients: 41 patients were diagnosed with chronic GvHD according to the revised Seattle criteria, 28 were classified as having extensive chronic GvHD and 13 were classified as having limited. The 1-year cumulative incidence was 43 +/− 9%. According to the NIH Consensus Criteria, 1 patient was reclassified as having late-acute GvHD, 20 patients as having overlap syndrome and 20 patients as having classic chronic GvHD. The late-acute consisted of late onset subtype. The 40 patients with classic chronic GvHD and overlap syndrome were graded as moderate (26 patients) and severe (14 patients) by NIH consensus criteria. The onset was classified as progressive in 4 cases, de novo in 27 cases, quiescent in 9 cases. The median number of organs involved was 3 (range 1–7), the majority of patients presented with skin and oral involvement, but also eyes, liver, joint, genitalia and gastro-intestinal damages were present – maximum severity of chronic GvHD according to organ manifestation is presented in figure 1. Twenty-seven out of 40 patients started a specific immunosuppressive treatment for chronic GvHD, noteworthy 21 patients restarted rapamycin (in combination with prednisone, or alone) with clinical benefit. In univariable analysis patients with overlap GvHD tended to present a lower overall survival (OS) compared to those with classic chronic GvHD (36% versus 63%, p 0.07). Patients with severe chronic GvHD at onset had a significantly lower OS compared to those with moderate chronic GvHD (19% versus 69%, p0.017). OS was significantly worse for patients with platelets counts below 100 g/l at onset of chronic GvHD (29% vs 67%, p0.003)– figure 2. Conclusion. This analysis confirms in haploidentical setting thrombocytopenia, overlap category and severe presentation as prognostic items for overall survival after allogeneic stem cell transplantation. Further investigations on implementation of immunosuppressive treatment strategy for high-risk GvHD patients (namely patients with overlap GvHD diagnosis and concomitant thrombocytopenia and/or progressive onset) are actually ongoing to enhance response and improve outcome. Disclosures: Bordignon: MolMed SpA: Employment. Bonini:MolMed S.p.A.: Consultancy.

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Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation: A Single Center Experience

Blood ◽

10.1182/blood-2019-129647 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2051-2051 ◽

Cited By ~ 1

Author(s):

Mindy Hsiao ◽

Anastasia Martynova ◽

George Yaghmour ◽

Chris Foss

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Optimal Dose ◽

Relapse Free Survival ◽

Free Survival ◽

Improved Outcomes ◽

The Mean ◽

Related Mortality

Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) has emerged as a popular alternative to traditional HLA-matched hematopoietic cell transplant. As the number of haplo-HCT's rises, investigating the factors that may affect outcomes is necessary in order to improve overall survival and reduce transplant-related mortality. The optimal dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though a range of 2 to 5.00x106 cells/kg is commonly used.Furthermore, the optimal dose of CD3+ cells is unknown however recent data has suggested less than 3.00x108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may help to improve outcomes in this setting. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 21) who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS) defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of both acute and chronic GVHD. Results: A total of 67 adult haplo-HCT recipients were reviewed. Of the patients evaluated, approximately 50% (n = 33) were male and 49% (n = 32) were female. The age range was 21-71 years old (median = 44), and the most common underlying hematologic disorders included AML (40%), ALL (38%), aplastic anemia (7.7%), and others (MDS, lymphoma, myelofibrosis, and HLH) (13.8%). 67% of patients received myeloablative conditioning regimens while 33% received reduced intensity regimens. 70% (n = 47) of patients received peripheral blood as a stem cell source with 30% (n = 20) receiving bone marrow. The mean CD34+ dose infused was 6.07x106 cells/kg and the mean CD3+ dose was 2.94x108 cells/kg. The mean time to recovery of platelets, neutrophils, and lymphocytes was 25, 18, and 37 days respectively. CD34+ stem cells ≥5.00x106 cells/kg was significantly associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not significantly associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77% respectively. Factors significantly associated with increased mortality included use of RIC regimen (p = 0.004) and disease status at time of transplant (p = 0.04). Cumulative incidence of GVHD was 63% (n = 42) with 33% (n = 22) and 30% of patients (n = 20) with acute and chronic GVHD respectively. Lack of mild chronic GVHD was associated with increased mortality (p = 0.0029) and use of a myeloablative regimen (p = 0.0029) was significantly associated with GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00x106 cells/kg (n = 24) and ≥10x106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00) respectively however this was not found to be significantly associated with increased incidence of GVHD, relapse, or mortality. Discussion: Our results demonstrate improved outcomes specifically 71% survived 1 year without experiencing at least 1 GRFS event compared with 24-35% reported by CIBMTR, Holtan et al 2015, and Solh et al 2016 with 3-year OS of 77% when compared with a previously reported 48%. The mean CD34+ cell dose of our population is higher than the standard range which may account for the improved outcomes however the dosing of CD34+/CD3+ cells were not significantly associated with our primary and secondary end-points. It was significantly associated, however, with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Furthermore, subgroup analysis of higher CD34+ dose did show a better 1-year OS though this was not statistically significant. Limitations of this study include small sample size and short follow-up period. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose in addition to comprehensive evaluation of immune recovery is warranted in order to improve haplo-HCT outcomes. Figure Disclosures Yaghmour: Jazz Pharmaceutical company: Consultancy, Speakers Bureau; Astella company: Speakers Bureau; Takeda: Speakers Bureau.

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Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease

Frontiers in Immunology ◽

10.3389/fimmu.2018.00010 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 11

Author(s):

Sina Naserian ◽

Mathieu Leclerc ◽

Allan Thiolat ◽

Caroline Pilon ◽

Cindy Le Bret ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Grading System ◽

Murine Models ◽

Host Disease ◽

Graft Versus Host ◽

Clinical Grading ◽

Acute Graft

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A grading system for predicting the prognosis of gastric cancer with liver metastasis

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab140 ◽

2021 ◽

Author(s):

Soshi Hori ◽

Michitaka Honda ◽

Hiroshi Kobayashi ◽

Hidetaka Kawamura ◽

Koichi Takiguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Overall Survival ◽

Liver Metastasis ◽

Confidence Interval ◽

Liver Metastases ◽

Hazard Ratio ◽

Maximum Diameter ◽

Grading System ◽

Computed Tomography Images

Abstract Objective The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. Methods This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. Results A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P < 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04–1.85): 1.69 (95% confidence interval: 1.27–2.27). Conclusions The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

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A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. II. Clinical manifestations

Blood ◽

10.1182/blood.v58.5.1021.1021 ◽

1981 ◽

Vol 58 (5) ◽

pp. 1021-1026 ◽

Cited By ~ 73

Author(s):

RT Schooley ◽

MA Flaum ◽

HR Gralnick ◽

AS Fauci

Keyword(s):

Hypereosinophilic Syndrome ◽

Clinical Manifestations ◽

Initial Therapy ◽

Multiple Organ ◽

Cytotoxic Agents ◽

Grading System ◽

Idiopathic Hypereosinophilic Syndrome ◽

Splenic Enlargement ◽

Organ Systems ◽

Clinical Grading

Abstract The idiopathic hypereosinophilic syndrome, a disorder characterized by peripheral blood and bone marrow eosinophilia associated with single or multiple organ system dysfunction attributable to tissue invasion by eosinophils has, in the past, been associated with an extremely poor prognosis. Recently, we reported the favorable impact of a therapeutic protocol consisting of prednisone and/or hydroxyurea on the morbidity and mortality of this syndrome. We have reviewed the clinical and hematologic features upon admission and the subsequent clinical courses of 32 patients with this disease referred to the NIH between 1965 and 1979 in an effort to determine which features suggest a more rapidly progressive course. A grading system based on 22 clinical features involving the 8 organ systems commonly affected by the illness was devised. The disease followed a more aggressive course in patients with evidence of cardiac or neurologic dysfunction at the time of initial NIH evaluation. Although splenomegaly, in and of itself, caused little morbidity, splenic enlargement at presentation appeared to be a predictor of a more aggressive course. The clinical grading system accurately predicted which patients would require no specific antihypereosinophilic therapy, which patients would respond adequately to corticosteroids, and which patients would require therapy with cytotoxic agents. It is proposed that this clinical grading system, and the hematologic grading system outlined in the accompanying report be used as aids in the selection of initial therapy in this group of patients.

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Abstract 5377: Low donor thymic output predicts increased incidence of extensive chronic GVHD and worse overall survival after TCD-matched sibling SCT

10.1158/1538-7445.am2012-5377 ◽

2012 ◽

Author(s):

Jan J. Melenhorst ◽

Zachariah A. McIver ◽

Haiyun Zheng ◽

Colin O. Wu ◽

Andrew Grim ◽

...

Keyword(s):

Overall Survival ◽

Chronic Gvhd ◽

Thymic Output ◽

Matched Sibling

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Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Blood ◽

10.1182/blood-2011-01-330217 ◽

2011 ◽

Vol 118 (2) ◽

pp. 456-463 ◽

Cited By ~ 57

Author(s):

Yoshihiro Inamoto ◽

Mary E. D. Flowers ◽

Stephanie J. Lee ◽

Paul A. Carpenter ◽

Edus H. Warren ◽

...

Keyword(s):

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Immunosuppressive Treatment ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Study Cohort ◽

Recurrent Malignancy ◽

Time Varying Covariates ◽

Risk Of Relapse

AbstractThis study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.

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Non-Myeloablative Allogeneic Transplantation in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.2759.2759 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2759-2759

Author(s):

Sabine Gerull ◽

Ute Hegenbart ◽

Martin Goerner ◽

Axel Benner ◽

Thomas Moehler ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Chronic Gvhd ◽

Autologous Transplantation ◽

Conditioning Regimen ◽

Progression Free Survival ◽

Allogeneic Transplantation ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Number Of Cycles

Abstract Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients. The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution. Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen. Acute toxicity was low with a WBC < 500/μl and platelets < 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved > 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006). We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.

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Multidrug Resistance-1 Gene Polymorphism Associated with the Outcomes after Allogeneic HLA-Identical Stem Cell Transplantation.

Blood ◽

10.1182/blood.v106.11.1757.1757 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1757-1757

Author(s):

Dong Hwan Kim ◽

Seok Bong Jeon ◽

Jin Ho Baek ◽

Nan Young Lee ◽

Jong Gwang Kim ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Multidrug Resistance ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cumulative Incidence ◽

Chronic Gvhd ◽

Mdr1 Gene ◽

Solid Organ ◽

Blood Concentrations

Abstract Background: The pharmacokinetic impact of multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNPs) has been already investigated in solid organ transplantation field, however, data is still lacking in an allogeneic stem cell transplantation (SCT) setting. Methods: A total of 82 patients receiving an allogeneic HLA-identical sibling (n=70) or unrelated SCT (n=12) with graft-versus-host disease (GVHD) prophylaxis of cyclosporine-A (CSA) plus methotrexate (MTX) were included in the current study. Two SNPs of MDR1 gene (C3435T and G2677T/A) were analyzed using PCR/RFLP assay. Results: As regards G2677T/A SNP, GG genotype showed a higher incidence of NRM compared to non-GG genotype (67% vs. 32%, p=0.0073), yet not C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival (OS) was significantly correlated with G2677T/A genotype (p=0.0048), yet not with C3435T (p=0.5041) or MDR1 haplotype (p=0.4086). However, no difference in the relapse incidence was noted according to G2677T/A, C3435T genotype or MDR1 haplotype. In a multivariate analysis, those patients without GG genotype at G2677T/A were found to have favorable prognosis in terms of OS (p=0.003) or NRM (p=0.031) along with occurrence of chronic GVHD (p<0.001 for OS, p=0.001 for NRM), standard disease risk (p=0.045 for OS) or acute grade 0,1 GVHD (p=0.019 for NRM). However, no correlation was found between the blood concentrations of CSA and MDR1 genotype and CSA neurotoxicity and MDR1 genotype. Conclusion: The G2677T/A genotype seemed to be associated with the transplantation outcomes, especially NRM. Further study is warranted to clarify its mechanism of MDR1 SNPs other than pharmacokinetic aspects. Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype

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