scholarly journals The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2657-2664 ◽  
Author(s):  
Bart L. Scott ◽  
Ted A. Gooley ◽  
Mohamed L. Sorror ◽  
Andrew R. Rezvani ◽  
Michael L. Linenberger ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
High Risk Disease ◽  
Risk Patients

Abstract Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

Applying the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) in Myeloablative MUD Transplants Predicts NRM and OS Using a Modified 2-Tier Scoring System.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1988-1988
Author(s):  
Tibor Kovacsovics ◽  
Byung Park ◽  
Brandon Hayes-Lattin ◽  
Jose F. Leis ◽  
Peter T. Curtin ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Scoring System ◽  
Clinical Decision Making ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Groups ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis

Abstract Background: The HCT-CI is a recently developed comorbidity score which has been adapted to hematopoietic stem cell transplantation, and identified 3 risk groups with increased non-relapse mortality (NRM) and lower overall survival (OS) (Blood2005;106:2912). We determined the HCT-CI score in a cohort of patients who underwent myeloablative MUD transplantation in a single arm, institutional trial assessing the efficacy of a combination of cyclosporine, methotrexate and prednisone for GVHD prophylaxis. Methods: The analysis included all patients undergoing MUD transplant from 1996–2006 who received GVHD prophylaxis with cyclosporine 2 mg/kg iv BID from day −2, methotrexate 15 mg/m2 iv on day +1 and 10 mg/m2 iv on days +3 and +6, and methylprednisolone 0.25 mg/kg iv BID beginning on day +7 and tapering from day +28. Patients were stratified by disease risk per CIBMTR classification. The comorbidities were obtained by retrospective chart review and scored according to the HCT-CI score. Results: 150 patients (median age 40) received the 3 drug-regimen, including 38% with low-, 34% with intermediate- and 28% with high-risk disease. Diagnoses included acute leukemia in 50%, MDS in 12%, CML in 15%, lymphoma in 18%, and multiple myeloma in 3.0%. Conditioning regimens included Cy-TBI in 64% and Bu-Cy in 21%. Source of stem cells was PBSC in 47.3% and marrow in 50.7%. HCT-CI scores of 0, 1–2 or ≥3 were found in 17%, 30% and 53% of patients evaluated. The majority of comorbidities were pulmonary (72%). With a median follow-up of 46 weeks, day 100 and 5-year OS were 82.7 and 33%, with a 23% and 50.4% cumulative incidence of NRM. Five year relapse-related mortality was 15.8%. Although higher HCT-CI scores were associated with increased NRM and decreased OS, no statistically significant differences were detected when using the published HCT-CI grouping of 0, 1–2 and ≥3. Unadjusted hazard ratio (HR) for inferior survival were 0.9 (CI 0.47–1.85, P=.79) and 1.65 (CI 0.885–3.090, P=.11) for scores 1–2 and ≥3, respectively. We then determined an alternate prognostic model based on 2 groups. Statistical modeling separated patients with a score of 0–3 (n=97, 64%) and ≥4 (n=53, 35.6%), with a 3 month and 5 year OS of 84% and 45% versus 52% and 10%, respectively (P<.0001). Cumulative incidence of day 100 and 5-year NRM was 16% and 38% versus 43% and 73%, respectively. Unadjusted HR for inferior survival was 2.77 (CI 1.816–4.225, P<.0001) for a score of ≥4. By multivariate analysis, only the HCT-CI score (P<.0001) and the disease risk per CIBMTR (P=.0058) were predictive of OS and NRM, but not age, CMV positivity, sex- or HLA-mismatch, or regimen. Conclusions: While our data confirm that the HCT-CI score is predictive of NRM and OS in a high-risk MUD transplant cohort, we were unable to detect statistically significant differences between the 3 risk groups defined in the original score. A modified 2-group scoring system readily stratified the patient population into low-risk and high-risk risk groups with scores of 0–3 and ≥4, respectively, that was predictive of OS and NRM. This simplified, 2-tiered scoring system will have utility in clinical decision-making and in defining patient populations eligible for clinical trials. Additional single and multi-institutional analyses will ultimately determine the optimal applications of the HCT-CI score.

Outcome Of Patients (pts) With Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 388-388 ◽  
Author(s):  
Elias Jabbour ◽  
Guillermo Garcia-Manero ◽  
Lianchun Xiao ◽  
Al Ali Najla ◽  
Asmita Mishra ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Lower Risk ◽  
Research Funding ◽  
Complete Response ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Cancer Center ◽  
Primary Resistance ◽  
High Risk Disease

Abstract Background HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4-6 months. The prognosis of pts with low and intermediate-1 risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure is not known. Aims To assess outcome of pts with low and intermediate-1 risk disease post HMA failure that might benefit from specific strategies or investigational agents. Methods Data from 423 pts with low (n= 141, 33%) and intermediate-1 risk disease (n=282, 67%) by IPSS score treated with HMA at MD Anderson Cancer Center (MDACC; n=144) and Moffitt Cancer Center (MCC; n=279) between 2000 and 2011 were analyzed. Results Median age was 69 years. 294 (69%) pts had a diploid cytogenetic analysis. 63 (15%) pts had therapy-related MDS. 282 (67%) pts received azacitidine, 87 (21%) decitabine, and 54 (12%) both. Median number of cycles of HMA administered was 6 (range, 1-64) for a median duration of therapy of 7 months (range, 1- 74). Best response to HMA was complete response (CR) in 39 (9%) pts, partial response (PR) in 13 (3%), a bone marrow CR in 6 (1%), and hematologic improvement (HI) in 90 (21%) pts. Pts had discontinued HMA because of primary resistance in 198 (47%) pts, loss of response in 141 pts (33%), intolerance in 13 pts (3%) and other reasons in 71 pts (17%). At the time of HMA failure, 81 (19%) pts transformed into acute myeloid leukemia (AML). Of the 302 remaining pts evaluable by IPSS, 67 (22%) pts were of low-risk, 158 (53%) of intermediate-1 risk, 48 (16%) of intermediate-2 risk, and 29 (9%) of high-risk disease. By the revised IPSS (R-IPSS), the percentage of pts with low, very low, intermediate, high, and very high risk disease were 11%, 29%, 30%, 20%, and 10%, respectively. By the MDACC global prognostic scoring system (MDGPSS) 18%, 35%, 29%, and 18%, of the pts were of low-risk, intermediate-1, intermediate-2, and high-risk disease, respectively. After a median follow-up of 16 months from HMA failure, 117 (28%) pts remained alive. The median overall survival (OS) was 15 months (95% CI: 12-18) with estimated 1- and 3-year OS rates of 55% and 27%, respectively. Both, the R-IPSS and the MDGPSS were predictive of survival post HMA failure (Table 1 ). Conclusion In the largest cohort of lower risk MDS pts treated with HMA, the outcome after HMA failure is poor. Treatment of those patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population. Disclosures: Lancet: Celgene: Research Funding. Sekeres:Celgene: Consultancy; Amgen: Consultancy. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

scholarly journals Killer Cell Immunoglobulin-like Receptor Ligand Matching Determines the Post-Transplant High Risk Groups Among Patients with Permissive HLA Mismatch in Unrelated Donor Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4566-4566
Author(s):  
Yoo Jin Lee ◽  
Joon Ho Moon ◽  
In Hee Lee ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Killer Cell ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Peripheral Blood Stem Cells

Abstract Background: Human leukocyte antigen (HLA) matching between donor and recipient is a key part of successful allogeneic hematopoietic cell transplantation (allo-HCT). The HCT from the unrelated donor (UD) with one allele/antigen mismatch (MM) can be as beneficial as HCT from perfectly matched donor. For the remaining patients, the donors with permissive mismatches may be the option. In HLA-mismatched transplantation, the patient and donor can also be mismatched for their killer cell immunoglobulin-like receptor (KIR) ligands that recognize allotypic determinants shared by certain HLA class I allele groups. Recent research has accumulated evidence of the role of each HLA locus and KIR ligand MM on clinical outcomes for UD-HCT. However, HCT outcomes of the patients with permissive MM depending on KIR ligand MM (KIR-L-MM) status remain obscure in UD-HCT. In the current study, we identified permissive and nonpermissive MM allele combinations and analyzed the effects of these mismatches in combination of KIR ligand mismatches in patients with acute myeloid leukemia (AML). Methods: A total of 438 patients with AML who underwent allo-HCT from UD from 2007 to 2014 were analyzed. Alleles of patients and donors at the HLA-A, -B, -C, and -DRB1 loci were identified by the high resolution DNA typing. Nonpermissive HLA allele combinations were defined as a significant HLA risk factor for severe acute graft-versus-host disease (aGVHD). KIR-L-MM among patient-donor pairs were searched in the Immuno Polymorphism Database available at www.ebi.ac.uk/ipd/kir. Results: Median age of the patients was 45 (range 15-60) years and 117 patients (40.4%) were female. Eighty-five (19.4%) patients were high risk at the time of HCT. Reduced intensity conditioning was performed in 131 patients (29.9%) and anti-thymocyte globulin was used in 324 patients (74.0%). Primary graft source was peripheral blood stem cells (n=369, 84.2%) and median 6.0 x 106/kg cells were infused. Severe aGVDH occurred in 43 patients (9.8%) and chronic GVHD (cGVHD) in 193 (44.1%). With median follow-up duration of 19 (range, 2-96) months, treatment-related mortality (TRM) occurred in 111 patients (25.3%), relapse in 119 (27.2%) and death in 214 (48.9%). Two-hundred sixty-four patients (60.3%) were HLA full matched in the 4 loci. Mismatches in HLA-A loci observed in 64 patients, HLA-B in 35, HLA-C in 98, and HLA-DRB1 in 60. Five nonpermissive MM pairs in 33 patients were identified as donor/patient pair: A*02:06/A*02:01, C*03:03/C*08:01, C*08:01/C03:04, C*08:01/C*15:02, and DRB1*04:03/DRB1*04:05. Among 98 patients with HLA-C loci MM, 16 patients showed KIR ligand MM (KIR-L-MM) as GvH direction, which was observed in the permissive MM group. Severe aGVHD occurred in 30.4%, 22.4%, 13.4%, and 10.8% in nonpermissive, permissive MM and KIR-L-MM, permissive MM and KIR-L-M, and full match group, respectively (p=0.003). The 3-year overall survival (OS) rate was inferior in permissive MM and KIR-L-MM group (30.0%) compared to full match (53.5%), permissive MM and KIR-L-M (51.8%), and nonpermissive (42.4%) group (p=0.067). The 3-year TRM was higher in permissive MM and KIR-L-MM group (57.5%) than full match (21.0%), permissive MM and KIR-L-M (27.7%), and nonpermissive (33.3%) group (p=0.006). In the multivariate analysis, high risk at HCT (HR 2.087, p<0.001), severe aGVHD (HR 3.851, p<0.001), and cGVHD (HR 0.321, p<0.001) were identified as variables affecting the OS. The following variables adversely affected on TRM: permissive MM and KIR-L-MM group (HR 2.699, p=0.007), severe aGVDH (HR 2.204, p=0.001), and cGVHD (HR 2.052, p<0.001). Non-permissive MM (HR 7.487, p=0.001) and CD34+ cells >6x106/kg (HR 4.113, p=0.017) were high risk factors on severe aGVHD. Conclusion: Permissive MM for HLA could be further classified into high risk groups with regard to TRM by KIR-L matching in UD-HCT. The evaluation of KIR-L matching is warranted to reduce unfavorable outcomes among the patients with permissive MM in UD-HCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

2015 ◽  
pp. e375-e380 ◽  
Author(s):  
H. Joachim Deeg
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
World Health ◽  
International Prognostic Scoring System ◽  
Small Subset ◽  
High Dose

Although high-dose chemotherapy may cure a small subset of patients with myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (HCT) is the only currently available modality that is curative in a large proportion of patients. Approximately 30% to 40% of patients with high-risk MDS and 60% to 80% of patients with low-risk MDS survive long-term in remission. Disease classification and risk assessment schemes, such as the World Health Organization (WHO) Prognostic Scoring System (WPSS), the Revised International Prognostic Scoring System (IPSS-R), and patient characteristics as assessed by the HCT Comorbidity Index (HCT-CI) or other scores, provide guidance for patient management. First, by defining the prognosis of patients without HCT, these tools help physicians decide who should and who should not be transplanted. Second, they predict at least in part how successful a transplant is likely to be. Pretransplant cytogenetics and marrow myeloblast count are the strongest risk factors for post-transplant relapse. The HCT-CI allows physicians to estimate the probability of nonrelapse mortality after HCT; recent data suggest that there is also a relationship to the development of graft-versus-host disease (GVHD). In general, the emphasis has shifted from high-dose therapy, aimed at maximum tumor-cell kill, to reduced-intensity conditioning (RIC), relying on the donor cell-mediated graft-versus-tumor (GVT) effects to eradicate the disease. GVT effects are most prominent in patients who also develop GVHD, especially chronic GVHD. Thus, ongoing work is directed at reducing GVHD while maintaining potent GVT effects and at exploiting the growing knowledge of somatic mutations for the development of targeted therapies.

scholarly journals Improved Survival of High Risk Patients with Parainfluenza Virus Following Hematopoietic Cell Transplantation: Role of Aerosolized Ribavirin

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5803-5803
Author(s):  
Isabelle T Nguyen ◽  
Sumana Shashidhar ◽  
Janice (Wes) M. Brown
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Respiratory Tract ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Parainfluenza Virus ◽  
High Risk Patients ◽  
Risk Patients ◽  
Tract Infections

Abstract Parainfluenza viruses (PIV) ARE associated with severe respiratory tract infections among immunocompromised patients. However, the most perplexing feature of PIV following hematopoietic cell transplantation (HCT) is the dichotomous nature of risk for life-threatening infection. Specifically, the vast majority of patients will not require treatment of any kind whereas a small subset appears to be at such high risk of death that it has been questioned if successful treatment is even possible. In 2007, we implemented a standardized approach to patients diagnosed with Parainfluenza virus (PIV) following HCT at Stanford University Medical Center (Fig 1) based on the need for supplemental oxygen and/or specific risk factors. We performed both a prospective analysis of cases of lower respiratory tract infection and a retrospective review of all 2495 patients transplanted during this period. The epidemiology, risk factors, clinical status, and outcome of the 115 PIV patients using this protocol from September 2007 through May 2015 shows that prudent, risk-stratified application of antiviral therapies in can result higher survival rates among patients with PIV post-HCT. Moreover, high risk patients who received aerosolized ribavirin had a lower mortality rate than those who were either not treated or received oral ribavirin. Disclosures No relevant conflicts of interest to declare.

International Working Group Scores Predict Post-Transplant Outcomes In Patients with Myelofibrosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3085-3085 ◽  
Author(s):  
Bart Lee Scott ◽  
Ted A. Gooley ◽  
Michael L. Linenberger ◽  
Brenda M. Sandmaier ◽  
David Myerson ◽  
...  
Keyword(s):  
High Risk ◽  
Working Group ◽  
Scoring System ◽  
Prognostic Model ◽  
Low Risk ◽  
Post Transplant ◽  
International Working Group ◽  
High Risk Disease ◽  
Risk Patients ◽  
History Of

Abstract Abstract 3085 The International Working Group (IWG) has determined that prognosis in myelofibrosis is predicted by a scoring system that includes the following parameters: age > 65 years, constitutional symptoms, hemoglobin < 10 g/dL, leukocyte count > 25 × 109/L and circulating peripheral blasts ≥ 1%. Based on these factors patients may be placed into 4 separate categories: low, intermediate-1, intermediate-2 or high risk. The median survivals of these 4 groups are 135, 95, 48 and 27 months, respectively. The IWG scoring system has been validated in a dynamic prognostic model. However, there have been no publications evaluating the use of the IWG prognostic model in patients with myelofibrosis who receive hematopoietic cell transplantation (HCT). We performed a retrospective review of 181 patients with a diagnosis of myelofibrosis who underwent HCT at the Fred Hutchinson Cancer Research Center between March, 1990 and November 2009. Twelve patients received an autologous transplant and 169 patients underwent an allogeneic transplant using an HLA-matched related (78), syngeneic (3), HLA-mismatched related (4), HLA-matched unrelated (66) or HLA-mismatched unrelated (18) donor. The median age at time of HCT was 51 (range: 12–78) years. Among the 169 patients who received allogeneic transplants, conditioning regimens consisted of oral busulfan, 16 mg/kg (136); oral busulfan, 7 mg/kg with TBI 12 Gy (9); TBI 12–13 Gy (4); Melphalan, 140 mg/kg (3); Fludarabine, 90 mg/m2 with TBI 2–4 Gy (16); and Treosulfan, 42 gm/m2 with Fludarabine, 150 mg/m2 (1). GVHD prophylaxis consisted of cyclosporin/methotrexate (99), tacrolimus/methotrexate (49), cyclosporin/mycophenolate (14) or tacrolimus/mycophenolate (4). We were able to obtain the full set of parameters involved in calculating the IWG score in all 181 patients. Historical records pre-transplant and arrival records prior to transplant were reviewed. Patients were assigned to the highest possible IWG score based on age at time of HCT, history of constitutional symptoms, hemoglobin < 10 g/dL or transfusion dependence at time of transplant, history of leukocyte counts > 25 × 109/L, and history of peripheral blasts ≥ 1%. Based upon these parameters, there were 21 patients with low risk, 48 patients with intermediate-1, 54 patients with intermediate-2, and 58 patients with high risk disease. The IWG score was highly predictive of survival in the post-transplant setting with a hazard ratio (HR) of 4.4 (95% CI 1.6–12.5, p=0.005) for mortality in high risk patients compared to low risk patients. Patients in the low risk category had a significantly lower risk of relapse HR=0 (95% CI 0, p=0.046) in comparison to patients with high risk disease. In addition, patients with high risk disease had a significantly greater risk of transplant related mortality HR=3.7 (95% CI 1.3–11, p=0.016) in comparison to patients with low risk disease. This is the first examination of post-transplant outcomes by the pre-transplant IWG score. This analysis suggests that patient and disease characteristics considered in the IWG score and shown to be of prognostic significance at diagnosis also predict post-transplant survival. These findings, with a follow-up extending to two decades, indicate that while transplantation was curative for a proportion of patients, it could not completely overcome the risk conveyed by pre-transplant risk factors. It is our hope that future studies will use this information to address the optimal timing of appropriate interventions including HCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1398-1408 ◽  
Author(s):  
H. Joachim Deeg ◽  
Bart L. Scott ◽  
Min Fang ◽  
Howard M. Shulman ◽  
Boglarka Gyurkocza ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
International Prognostic Scoring System ◽  
Disease Category ◽  
Stem Cell Source ◽  
The Impact ◽  
Monosomal Karyotype

AbstractClonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.

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