Survival Advantage with Hypomethylating Agents In Patients with Higher Risk Myelodysplastic Syndrome

Abstract Abstract 1859 Background: Two hypomethylating agents, azacitidine and decitabine, are active in myelodysplastic syndrome (MDS) and both drugs have been approved for the treatment of MDS in Korea. In this retrospective analysis, we tried to analyze the effects of hypomethylating agents on the clinical outcomes of the patients with MDS. Methods: A total of 385 patients, who were diagnosed as MDS at the Asan Medical Center between July 1992 and March 2010, were included in this study. We divided the patients into three treatment groups such as hypomethylating therapy (HMT, n=92), intensive chemotherapy (IC, n=15), and supportive care (including low-dose cytarabine and immunosuppressive treatment, SC, n=278). Primary end points of this study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. All survival data were censored at the time of hematopoietic cell transplantation (HCT) to eliminate the influence of HCT on survivals. The difference of survivals was compared using time updated Cox model because times from diagnosis of MDS to treatment (HMT or IC) were various. Results: Baseline clinico-laboratory features were not significantly different between 3 treatment groups (HMT vs. IC vs. SC) in regard to sex, age, WHO subtype, and IPSS risk category. Among 83 patients in the HMT group, 39 (47.0%) attained any response to HMT including complete response, partial response, marrow complete response, and hematologic improvement. Survival data were the followings: OS, HMT vs. IC vs. SC, median 62.5 vs. 16.7 vs. 21.0 months; PFS, median 37.7 vs. 13.8 vs. 17.8 months. Multivariate analyses by stratified time updated Cox model showed that hazard ratio (HR) of HMT compared to SC was 1.029 (95% CI, 0.670–1.582, P=0.895) for OS and 0.539 (95% CI, 0.362–0.803, P=0.002) for PFS. When we performed subgroup analyses in lower risk disease (IPSS Low/Intermediate-1) and higher risk disease (IPSS Intermediate-2/High), the effects of HMT on survivals were different by the risk stratification of MDS. In lower risk MDS, there were no survival benefits of HMT compared to SC (OS, median 53.9 vs. 39.8 months, HR 1.570, P=0.108; PFS, median 37.7 vs. 52.5 months, HR 0.880, P=0.633), whereas both OS and PFS were significantly longer in HMT compared to SC (OS, median 137.9 vs. 5.9 months, HR 0.289, P=0.043; PFS, median 80.2 vs. 0.9 months, HR 0.154, P<0.001). Conclusion: Our data suggested that hypomethylating therapy could improve the survivals (OS and PFS) of the patients with higher risk MDS. Disclosures: No relevant conflicts of interest to declare.

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microRNA-22 and TET-2 Mutation in Myelodysplastic Syndrome Patients Treated with Hypomethylating Agents

Blood ◽

10.1182/blood-2018-99-117943 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5127-5127

Author(s):

Seong Kyu Park ◽

Se Hyung Kim ◽

Sung Hee Lim ◽

Chan Kyu Kim ◽

Jong-Ho Won ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Lower Risk ◽

Conflicts Of Interest ◽

Risk Group ◽

Hypomethylating Agents ◽

Poor Survival ◽

Leukemic Transformation ◽

Clinical Role ◽

Aberrant Expression ◽

Tet2 Mutation

Abstract Background: MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. Some reports suggested that aberrations in the miR-22-TET2 regulatory network are common in myelodysplastic syndrome (MDS) and leukemia, and its aberrant expression correlates with poor survival. We attempted to identify the clinical role of miR-22 and TET-2 in patients with myelodysplastic syndrome. Materials and Methods: A total of 41 MDS patients who treated with hypomethylating agents were recruited. Real time RT-PCR was performed to assess the expression levels of miR-22 and TET-2 mutation in bone marrow samples at the time of diagnosis. And we investigated the relationship between its results and clinical outcomes. Results: TET2 mutation frequency in the higher risk group based the IPSS and IPSS-R was lower than that of lower risk group (11.1% vs 38.1%). miR22 expression was also down-regulated in higher risk group (higher risk: 1.70 ± 0.96 vs lower risk: 3.14 ± 1.38, p=0.006). TET2 mutation seemed to be different according to the responsiveness to hypomethylating agents. TET2 mutation, IPSS, and IPSS-R were significantly associated with the risk of leukemic transformation. Patients with an decreased value in the consecutive assessment of miR-22 at the time of diagnosis and 3 months after initial treatment tended to be associated with poor survival outcome (survival rate at 3 years: 18.2% vs 35.1% for patients with an increase, p=0.168). Prognostic factors for survival included TET-2 mutation, cytogenetics, IPSS or IPSS-R, and leukemic transformation. Conclusion: miR-22 expression and TET2 mutation had a clinical impact on outcomes in MDS patients treated with hypomethylating agents. And these biomarkers might have a potential as a prognostic factor for MDS patients. Disclosures No relevant conflicts of interest to declare.

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Role Of Hypomethylating Agents For Patients With Lower-Risk Myelodysplastic Syndrome Defined By IPSS and IPSS-R

Blood ◽

10.1182/blood.v122.21.2782.2782 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2782-2782

Author(s):

Joon Ho Moon ◽

Sang Kyun Sohn ◽

Jae Sook Ahn ◽

Yeo-Kyeoung Kim ◽

Hyeoung Joon Kim ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Lower Risk ◽

Conflicts Of Interest ◽

Risk Groups ◽

International Prognostic Scoring System ◽

Hypomethylating Agents ◽

Risk Patients ◽

Very High ◽

Prognostic Power

Abstract Background International Prognostic Scoring System (IPSS) is commonly used to distinguish various subgroups of myelodysplastic syndrome (MDS) patients with different prognosis and to make a therapeutic decision. However, the classic IPSS, defining lower-risk as low and intermediate-1 IPSS, seems to be insufficient to discriminate the prognostic groups of lower-risk MDS. Recently, IPSS was updated into the revised score (IPSS-R) to refine the IPSS by reassessing the major predictive features of MDS. The hypomethylating agents (HMA) are usually recommended for patients with lower-risk MDS who is not responsive to other therapies. However the role of HMA for the patients with lower-risk IPSS are still on debate. This study was conducted to find the rationale to treat HMA for the patients with lower-risk IPSS and to know whether IPSS-R further discriminate the prognosis of patients treated with HMA. Methods The data of 334 patients diagnosed with MDS lower-risk defined by IPSS after Jan 2006 were retrospectively reviewed. Lower-risk IPSS was revised into IPSS-R to know whether it could further discriminate the prognosis of this group of patients. The prognosis of lower-risk by IPSS and IPSS-R were analyzed in terms of overall survival (OS) and prognostic power was calculated with time-dependent Cox-hazard models. To define the role of HMA for patients with lower-risk IPSS, we categorized the lower risk patients into No-HMA group, early HMA group (HMA within 2 mo.), and late HMA group (HMA after 2 mo). Results Out of 334 lower-risk patients (39 low and 295 intermediate-1), 195 patients (58.4%) were treated with HMA (azacitidine 163, decitabine 32). Median time to HMA treatment was 43 days (range 0-1778 days). 3yr-OS rate was not significantly different between HMA group (43.1¡¾4.2%) and non-HMA group (62.3¡¾5.9%) (p=0.099). Early HMA treatment (3yr-OS 36.4¡¾5.4%) didn't show survival benefits compared to late HMA group (54.6¡¾6.3%) or no-HMA group (62.3¡¾5.9%) (p=0.003). Plus, HMA response (CR/PR/HI) didn't guarantee OS benefits: 3yr-OS of 45.2¡¾7.4% in responders (CR/PR/HI, n=74) and 43.4¡¾5.0 in non-responders (SD/PD, n=121) (p=0.239). Among 39 patients with IPSS low, 11 patients (28.2%) were revised into IPSS-R very low, 24 (61.5%) into low, 3 (7.7%) into intermediate, and 1 (2.6%) into high. Among 295 patients with IPSS intermediate-1, 4 patients (1.4%) were revised into IPSS-R very low, 84 (28.5%) into low, 133 (45.1%) into intermediate, 71 (24.1%) into high and 3 (1.0%) into very high. IPSS-R could further discriminate the IPSS lower-risk patients with regard to OS: 3yr-OS rates of 100% in very low, 64.5¡¾5.9% in low, 46.1¡¾5.5% in intermediate, 26.1¡¾6.6% in high, and 0% in very high (p<0.001). The survival benefits of HMA for lower risk groups (very low and low) defined by IPSS-R (n=123) was not defined in the current study, where 3yr-OS was 83.8¡¾6.4% in no-HMA group (n=60) vs. 60.5¡¾7.1% in HMA group (n=63) (p=0.198). Conclusion The prognosis of the patients with lower-risk IPSS (low and intermediate-1) were successfully refined by IPSS-R. The IPSS intermediate-1 risk was heterogeneous group, which subdivided into very low to very high by IPSS-R. However, the beneficial effect of HMA for patients with lower-risk MDS, defined by IPSS (low and intermedite-1) and IPSS-R (very low and low), should be elucidated in the future studies. Disclosures: No relevant conflicts of interest to declare.

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Time Changes In Predictive Power Of MDS Prognostic Scores – Effects On Revised Scores Such As The IPSS-R, Impact Of Age

Blood ◽

10.1182/blood.v122.21.1544.1544 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1544-1544 ◽

Cited By ~ 2

Author(s):

Michael Pfeilstöcker ◽

Heinz Tüchler ◽

Julie Schanz ◽

Guillermo Sanz ◽

Guillermo Garcia Manero ◽

...

Keyword(s):

Lower Risk ◽

Prognostic Value ◽

Conflicts Of Interest ◽

Scoring Systems ◽

Prognostic Scores ◽

Risk Category ◽

Prognostic Scoring Systems ◽

Prognostic Power ◽

Risk Categories ◽

Over Time

Abstract Introduction New, refined prognostic scoring systems have been established for MDS. Most scores assess prognosis at time of diagnosis assuming stable prediction over time. Earlier studies have shown moderate loss of prognostic power over time in scores using clinical parameters whereas cytogenetic scores maintained prognostic power, scores including comorbidity had shown gain of prognostic power (Pfeilstöcker et al, 2012). The aim of this multicenter retrospective study was to assess the relative stability of the newly developed scoring systems over time, to compare and explain observed time-related losses of prognostic power, and to discuss their clinical implications. Methods This study is based on 7212 untreated (no disease modifying treatment) MDS patients from multiple institutional databases of the IWG-PM, which generated the IPSS-R (Greenberg et al, 2012). Patient characteristics were well comparable with other populations: median age 71 years, male gender 60 %, median overall survival 3.8 years (range 3.7-4.0), median time to AML transformation not reached with 25% of patients transforming to AML after 6.8 years. Patients were diagnosed and classified by FAB and WHO; cytogenetics were classified by original IPSS subtypes and by the recently refined proposal integrated into the IPSS-R (Schanz et al, 2012). The following scores were analysed for their stability over time: IPSS, IPSS-R, WPSS variants, cytogenetic scores, age, performance status and other differentiating features of the IPSS-R. Time variations were described by the Cox-zph-test, and by applying Dxy, a measure of concordance, for censored data at separate observation periods. Results In line with previous observations, loss of prognostic power occurred over time after diagnosis in all scoring systems. While for the entire population the risk between adjacent IPSS-R risk categories differs by ∼80%, for patients observed at least 1 year the increase is ∼66%, and for those observed 4 years it is only ∼25%. The IPSS-R and particularly its age-including version (the IPSS-RA) retained the highest prognostic values compared to all other scoring systems at all time points. Dxy for IPSS-R: at diagnosis 0.43, 1 year 0.35, 2 years 0.27, 4 years 0.14. Including age, as in the IPSS-RA, was associated with less loss of prognostic power over time: Dxy at diagnosis 0.46, 1 year 0.38, 2 years 0.31, 4 years 0.22. For the IPSS and WPSS (available for the latter in only 33% cases), these values were: 0.37, 0.30, 0.22, 0.11 and 0.44, 0.36, 0.29, 0.18 respectively. Considering risk categories, the risk remained fairly constant over time for the lower risk categories in every analyzed scoring system, while the risks in the higher risk categories were especially high in the second half of the first year after diagnosis, diminishing thereafter, thus reducing the prognostic value of these categories over time. To determine whether statistical weights optimized for each time period would alter these results, time-specific weights were applied, which did not demonstrate substantially different prognostic values from the basic model analysis. Particularly good retention of prognostic power was found in the lower risk categories over time. The lesser retention of prognostic power in the higher risk categories appeared related to loss of a larger portion of these patients over time due to their deaths or being censored by their beginning treatment. For the IPSS-R intermediate risk category patients, the prognosis for survival approached the “high” category ∼3 years after diagnosis, while it remained intermediate regarding their risk of AML transformation. Conclusions These data demonstrate that a degree of attrition of prognostic value occurred over time from diagnosis for all of the assessed MDS prognostic scoring systems. The IPSS-R, particularly the age-inclusive IPSS-RA, best retained such prognostic capability over time for the untreated patients analyzed. Disclosures: No relevant conflicts of interest to declare.

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Retrospective Case Series Study of Hypomethylating Therapy in IPSS Lower-Risk Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v128.22.1992.1992 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1992-1992

Author(s):

Han-Seung Park ◽

Je-Hwan Lee ◽

Yoo-Jin Kim ◽

Sang Kyun Sohn ◽

Sung-Soo Yoon ◽

...

Keyword(s):

High Risk ◽

Survival Data ◽

Lower Risk ◽

Conflicts Of Interest ◽

Case Series ◽

Retrospective Case ◽

Retrospective Case Series ◽

Case Series Study ◽

Prognostic Indices ◽

Series Study

Abstract Introduction: The IPSS has been widely used for risk stratification in myelodysplastic syndromes (MDS), and patients with IPSS low and intermediate-1 scores are designated as having lower-risk (LR) MDS. Despite its utility, the outcomes of patients with LR disease defined by IPSS are variable and a subset of patients experience inferior than expected outcomes. Treatment with hypomethylating agents is the standard of care in higher-risk MDS, but there have been little data for hypomethylating therapy in LR MDS. We retrospectively collected and analyzed the data related to hypomethylating therapy in IPSS LR MDS from 12 Korean institutes. Patients and Methods: A total of 610 patients, who were treated with azacitidine or decitabine for IPSS LR MDS, were included in this retrospective case series study. All patients received azacitidine (7-day) or decitabine (5-day). Both regimens were repeated every 4 weeks. The overall response rate (ORR) included rates for complete response (CR), partial response (PR), marrow CR (mCR), and stable disease (SD) with hematologic improvements (HI). For 139 patients who underwent allogeneic hematopoietic cell transplantation (HCT), all survival data were censored at the time of HCT. Results: Median age was 63 (19-84) years. IPSS category was low in 44 and intermediate-1 in 566. The patients were reclassified with other scoring systems including revised IPSS (R-IPSS), WPSS, and LR-PSS, and between 21.8% and 37.7% of patients were identified as having high or very high risk features by the other prognostic indices. Patients received azacitidine (n=436) or decitabine (n=174) for a median of 5 (1-46) courses. ORR was 51.3% (CR 78, PR 12, mCR with HI 27, mCR without HI 20, and SD with HI 176). 294 patients (48.2%) showed any HI. Median OS was 2.35 years and patients with HI had significantly longer OS than those without HI (P=0.001). Our case series patients were well stratified in terms of OS by R-IPSS (P=0.001), WPSS (P<0.001), and LR-PSS (P<0.001). Conclusion: IPSS LR MDS included a broad range of prognostic implications. Hypomethylating therapy brought varying degrees of response in about half of the patients with IPSS LR MDS. The patients who had high risk features with other prognostic indices showed poor OS and allogeneic HCT should be considered during the course of hypomethylating therapy in these patients. Disclosures No relevant conflicts of interest to declare.

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High Residual Allelic Burden Increases Leukemic Transformation Irrespective of Clinical Response in Patients with Lower Risk Myelodysplastic Syndrome Treated with Azacitidine

Blood ◽

10.1182/blood-2019-130428 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4263-4263

Author(s):

Joon Ho Moon ◽

Hee Jeong Cho ◽

Dong Won Baek ◽

Sang Kyun Sohn ◽

Jae-Sook Ahn ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Clinical Response ◽

Cumulative Incidence ◽

Lower Risk ◽

Conflicts Of Interest ◽

Rank Test ◽

Leukemic Transformation ◽

Mutation Group ◽

Allelic Burden

Background: Hypomethylating agents (HMAs) are used to treat patients with lower-risk myelodysplastic syndrome (LR-MDS) relapsing after the use of hematopoietic cytokines or presenting initially with more than two lineages of cytopenias. However, the significance of underlying genetics and allelic burden changes after HMAs are still under investigation. This study investigated the effects of allelic burden changes on the long-term outcomes in LR-MDS patients treated with HMAs. Methods: This study included 61 patients with LR-MDS treated with azacitidine. Bone marrow samples were taken at diagnosis and follow-up after median 4 cycles. Targeted deep sequencing on a custom myeloid gene panel of 84 genes (Agilent SureSelect) was performed on trios of T-cell, pre-HMA, and post-HMA samples on 61 LR-MDS patients. Patients were divided into groups according to the post-HMA variant allele frequency (VAF): low-VAF (< 2%), high-VAF (≥ 2%), and no-mutation group (absence of mutations at diagnosis and follow-up). Overall survival (OS) was defined as the time from the azacitidine treatment until death from any cause, which was analyzed using the Kaplan-Meier method and the groups were compared using the log-rank test. The cumulative incidence of AML was calculated using the Gray method, considering death without AML as a competing risk. Fine-Gray proportional hazard regression with a competing event was used to identify risk factors for the incidence of AML. Results: Median age was 67 years (range 31-81), and 41 patients (67%) were male. IPSS risk group were low in 2 patients (3%) and intermediate-1 in 59 (97%). At diagnosis, 38 patients harbored at least one mutation. Most frequently mutated genes were ASXL1 (n=11, 18%), TET2 (n=10, 16%), and SRSF2 (n=7, 11%) followed by RUNX1, SF3B1, U2AF1, IDH2, and DNMT3A. Azacitidine was administered median 8 cycles (range 2-44). The overall response (CR, PR, HI) was achieved in 18 patients (30%). With median follow-up duration of 31 months (range 4.7-135 months), leukemic transformation occurred in 11 patients (18%). Mutational allelic burdens were decreased from median 20.9% (range 0.1-67.2) to 11.0% (range 0.0-74.9%). At follow-up, 5 patients were low-VAF group and 33 were high-VAF group. OS rate was not different between the low-VAF and high-VAF group (50% vs 46% at 3 years; p=0.80). Three-year cumulative incidence of AML was higher in high-VAF group compared to low-VAF (0%) and no-mutation group (4.8%, p=0.02). However, non-leukemic mortality was higher in low-VAF group than no-mutation group (60% vs 23%, p=0.09), which explains similar OS rate between low-VAF and high-VAF group. In the multivariate analysis, high-VAF was an independent predictive factor for an AML transformation in LR-MDS patients treated with azacitidine (HR 5.20, p=0.04). Conclusion: The current study showed that the high residual allelic burden is associated with an increased AML transformation in LR-MDS patients treated with azacitidine, irrespective of the clinical response. The higher non-leukemic mortality explains inferior OS in low-VAF group compared to no-mutation group. Figure Disclosures No relevant conflicts of interest to declare.

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Azacitidine Is Effective in Patients with Intermediate-2 / High IPSS Risk Myelodysplastic Syndrome Managed in Community Based Practice: Preliminary Data From the Spanish Azacitidine Compassionate Use Registry.

Blood ◽

10.1182/blood.v114.22.4835.4835 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4835-4835

Author(s):

Regina Garcia ◽

José Ramón González ◽

Alicia Bailen ◽

Jose F Falantes ◽

Joaquin Sanchez ◽

...

Keyword(s):

Clinical Trials ◽

Myelodysplastic Syndrome ◽

Preliminary Data ◽

Conflicts Of Interest ◽

Performance Status ◽

Complete Response ◽

Compassionate Use ◽

Community Based ◽

Ecog Performance Status ◽

Female Ratio

Abstract Abstract 4835 Background Myelodysplastic syndrome (MDS) is comprised of a group of heterogeneous hematological disorders. Although the decision regarding treatment of a patient with MDS is based on performance status, age, patient preference and concomitant illnesses, NCCN-recommended treatment approaches vary according to IPSS risk score. Azacitidine (AZA) is a hypomethylating agent recently approved in Europe for the treatment of MDS. AZA was available in Spain under compassionate use before its regulatory approval and marketing authorization from the Spanish Medicines Agency in May 2009. Material and Methods We present the preliminary analysis of the clinical data from a longitudinal, multicenter Spanish patient registry. Data on the disease course and management of patients with MDS treated with AZA under compassionate use conditions were retrospectively collected from community-based hematology clinics. As of August 1, 2009, 65 patients with intermediate-2 / high IPSS-risk MDS diagnosed according to WHO criteria had been included. Results At baseline the median age was 69 years, the male/female ratio was 60/40, and the majority of patients had primary MDS (56 patients; 88%) and an ECOG performance status of 0-1 (43 patients; 67%). The most frequent initial dose of AZA applied was 75 mg/m2 (53 patients, 83%), and the most common dosing schedules were as follows: days 1-7 (82%), and days 1-5 and 8-9 (5%) in a 28-day cycle. AZA was administered mostly subcutaneously (56 patients, 89%). The mean number of cycles administered was 6 (range 2-29). The overall treatment response was 59% (International Working Group 2006 criteria): 16% complete response, 13% complete bone marrow response, 13% partial response and 18% hematological response. In addition, 23% achieved stable disease. AZA was generally well tolerated. The grade 3/4 adverse events documented in these patients, regardless of their relationship to active treatment, were neutropenia (37%), thrombocytopenia (26%), anemia (17%), febrile neutropenia (8%), rash (2%), vomiting or nausea (2%), and constitutional symptoms (2%). Conclusion These preliminary data do not differ from those previously obtained from clinical trials (Silverman et al 2006, Fenaux et al 2009). Our results demonstrate that in a community-based setting, patients with intermediate-2 / high-risk MDS respond to treatment with AZA. In line with previous clinical trials, we expect this could point to a better prognosis for MDS patients in Spain, with prolonged survival and a better quality of life. Disclosures No relevant conflicts of interest to declare.

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Evaluation of Tacrolimus Combined With Corticosteroids vs Modified Ponticelli Regimen as Treatments for Refractory Primary Membranous Nephropathy

Global Journal of Health Science ◽

10.5539/gjhs.v10n12p63 ◽

2018 ◽

Vol 10 (12) ◽

pp. 63

Author(s):

Elkin Navarro-Quiroz ◽

Gustavo Aroca-Martinez ◽

Alex Domínguez-Vargas ◽

María José Alonso-López ◽

Rebeca Alvarado-Echeverría ◽

...

Keyword(s):

Treatment Response ◽

Membranous Nephropathy ◽

Analytical Study ◽

Oral Corticosteroid ◽

Response Rate ◽

Immunosuppressive Treatment ◽

Complete Response ◽

Treatment Groups ◽

Syndromic Diagnosis

OBJECTIVE: To evaluate the immunosuppressive treatment response to modified Ponticelli regimen (MPR) and oral corticosteroid (OC) plus tacrolimus (TAC) in patients with primary membranous nephropathy (PMN). METHODS: Retrospective cohort analytical study. Adults patients (>18 years old) with diagnosis of refractory PMN (>50% increase in serum creatinine or a level >1.5mg/dl or proteinuria refractory to 6 months of supportive treatment), proved by renal biopsy and immunofluorescence between 2008 and 2016 from the Nephropathy Registry of Colombia (NEFRORED©) were included. Immunosuppressive treatment response was evaluated from baseline to 6 months after the start of therapy. RESULTS: 128 patients with PMN were included, of which 74 (57%) were female. The most frequent syndromic diagnosis was nephrotic syndrome 90 (70%), followed by asymptomatic urinary disorders 31 (25%). Chronic kidney disease manifested concomitantly in 7 (5%) patients. At the end of 6 months, 86 (67%) cases achieved some degree of remission: 23 (18%) complete response (CR) and 63 (49%) cases with partial response (PR), while 42 (33%) cases did not achieved remission. In the TAC+OC group, CR and PR were seen in 14 (20%) and 33 (47%) patients, respectively; and 9 (16%) and 30 (51%) patients in the MPR group, respectively. No statistically significant differences were found when comparing the immunosuppressive treatment response rate with both treatment groups (p > 0.05). CONCLUSIONS: In the PMN, both immunosuppressive treatments (TAC+OC vs MPR) are comparable. We suggest a clinical follow-up of the anti-PLA2R/THSD7A titres at 6/12 months to be correlated with renal function in subsequent studies.

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Hypoplastic Myelodysplastic Syndrome (h-MDS) Is a Distinctive Clinical Entity with Poorer Prognosis and Frequent Karyotypic and FISH Abnormalities Compared to Aplastic Anemia (AA).

Blood ◽

10.1182/blood.v114.22.3199.3199 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3199-3199 ◽

Cited By ~ 1

Author(s):

Youngil Koh ◽

Hye Ryun Lee ◽

Eun Young Song ◽

Hyun Kyoung Kim ◽

Inho Kim ◽

...

Keyword(s):

Aplastic Anemia ◽

Conflicts Of Interest ◽

Immunosuppressive Treatment ◽

University Hospital ◽

P Value ◽

Risk Category ◽

Prognostic Impact ◽

Complex Karyotype ◽

Karyotypic Abnormality ◽

Disease Subtype

Abstract Abstract 3199 Poster Board III-136 Differences between hypoplastic MDS (h-MDS) and aplastic anemia (AA) are not defined. Role of karyotype and fluorescent in situ hybridization (FISH) in these diseases is not established. Medical record review at Seoul National University Hospital between 1990 and 2008 was performed. Patients diagnosed as either h-MDS or AA based on morphology was reviewed. We assessed overall survival (OS) and leukemic conversion. 369 AA and 40 h-MDS patients (median age 39 years, range 15-82) were analyzed. 235 and 165 patients underwent karyotyping and FISH at diagnosis respectively. Compared to AA, karyotypic abnormality, 5q deletion, trisomy 8 and trisomy 1q FISH abnormalities were more frequently found in h-MDS. Median OS of h-MDS was shorter than AA (60 vs. 219 months, p<0.001) with prognosis of h-MDS falling between severe and very severe AA. Patients with h-MDS had more frequent leukemic conversion (p<0.001) than AA patients. Karyotypic abnormality was not prognostic in AA (p=0.225). For h-MDS, complex karyotype and trisomy 1q FISH abnormality predicted poor prognosis. The prognosis of h-MDS falls between severe and very severe AA. h-MDS accompanies frequent karyotypic and FISH abnormality and is prone to leukemic conversion. Complex karyotype and trisomy 1q FISH abnormality may have a prognostic role in h-MDS. Table 1 Characteristics of patients according morphologic classification in 409 patients Characteristics Aplastic anemia (N=369) Hypoplastic MDS (N=40) p-value Age (median) 38.0 49.5 0.005 Gender 0.846 Male 197 22 Female 172 18 White blood cell (mean) (/μL) 2724 3042 0.368 Reticulocyte count (mean) (%) 1.1 1.8 0.007 Hemoglobin (mean) (g/dL) 8.3 7.9 0.357 Platelet (mean) (/μL) 44130 109000 0.008 Severity of cytopenia* 0.007 Moderate 244 36 Severe 96 4 Very severe 28 0 PNH component NA Present 15 NA Absent 351 NA IPSS risk category NA Intermediate-1 NA 25 Intermediate-2 NA 4 High NA 1 Oxymetholone administration# 0.005 Yes 167 9 No 196 30 Immunosuppressive treatment# 0.005 Yes 114 4 No 249 35 Stem cell transplantation# 1.000 Yes 49 5 No 314 34 Figure 1 OS of patients according to disease subtype h-MDS had inferior OS compared to AA in general (A), and its prognosis falls between SAA and VSAA (B). h-MDS had shorter OS compared to AA even stratified by the degree of cytopenia. IPSS score had a prognostic impact on h-MDS (D). Figure 1. OS of patients according to disease subtype h-MDS had inferior OS compared to AA in general (A), and its prognosis falls between SAA and VSAA (B). h-MDS had shorter OS compared to AA even stratified by the degree of cytopenia. IPSS score had a prognostic impact on h-MDS (D). Disclosures No relevant conflicts of interest to declare.

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Treatment of Relapse After Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndrome: A Large-Scale Study On Behalf of the Société Française De Greffe De Moelle Et De Thérapie Cellulaire (SFGM-TC)

Blood ◽

10.1182/blood.v120.21.593.593 ◽

2012 ◽

Vol 120 (21) ◽

pp. 593-593

Author(s):

Romain Guièze ◽

Gandhi Damaj ◽

Marie Robin ◽

Mohamad Mohty ◽

Mauricette Michallet ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Supportive Care ◽

Large Scale ◽

Conflicts Of Interest ◽

Immunosuppressive Treatment ◽

Tumor Burden ◽

Hematopoietic Stem ◽

Satisfactory Outcome ◽

Cytoreductive Treatment ◽

The Impact

Abstract Abstract 593 Background: Treatment of patients with myelodysplastic syndrome (MDS) relapsing after allo-SCT remains disappointing and prognostic factors for outcome are still unclear. Several therapeutic approaches are offered to those patients including: palliative and supportive care, intensive chemotherapy (ICT), demethylating agents (DMA) and immunotherapy with either donor lymphocyte infusion (DLI) or second allo-SCT. The aim of this study was to identify predictive factors for outcome and to investigate the impact of different treatment groups on survival. Methods: We report a retrospective study on 137 consecutive MDS patients who relapsed after allo-SCT between Jul 1999 and March 2011 in 19 French and Belgian centers. Data quality was ensured using computerized discrepancy errors and vigorous on-site data verification of every single file. HLA matching was double-checked by the French Bone Marrow Donor Registry. Results: At diagnosis, 61 patients presented RA/RARS/RCMD, 27 RAEB1 and 49 RAEB2 according the WHO classification. Cytogenetic was unfavorable in 47 patients (35%) while 76 patients (57%) had IPSS Int-2 or High and 52 (39%) had progressed to a more advanced disease before allo-SCT. At transplant, 62 patients (47%) were considered responders (in CR or PR), while 70 were transplanted with progressive disease (untreated, stable without hematological improvement, relapsed or refractory disease). Patients received either myeloablative (MAC) (n=38) or nonmyeloablative (RIC) (n=99) conditioning. Source of stem cells was BM (n=40) or PBSC (n=97) from sibling (n=89) or allele well-matched unrelated (10/10) (n=48) donors. Median age at relapse was 57 years (range, 19–70). Patients aged <18 years and those who received graft from either cord blood or mismatched donor were excluded. Post-transplant relapse occurred after a median time of 6 months (range, 0.8–102). Of the 109 evaluable patients 62 (57%) had >= 10% of marrow blasts, of whom 38 had >= 20%. At the time of relapse, 61 patients were still under immunosuppressive treatment which was quickly stopped in all of them. For the analysis, patients were divided into three groups according to ultimate salvage received treatment as follows: palliative and supportive care (PSC-group) (n=42, 31%), cytoreductive treatment alone (CRT-group) [DMA (n=18, 13%) and ICT (n= 11, 8%)] and immunotherapy preceded or not by a CRT (IT-group) [DLI (n=48, 35%) and second allo-SCT (n=18, 13%)]. With a median follow-up of 33 months from the relapse, estimated 2-year overall survival was 2.4%, 6.7% and 30.3% for the PSC-group, CRT-group and IT-group, respectively (p<.0001). In multivariate analysis, 3 independent factors have been identified: the absence of immunotherapy HR= 1.45 [95% IC= 1.25–1.69, p<.0001], early relapse within 6 months after transplant, HR=2.71 [95% IC= 1.66–4.45, p<.0001] and marrow blasts at relapse >= 10%, HR=2.56 [95% IC= 1.55–4.22, p<.0001]. Conclusion: This study shows that salvage immunotherapy (DLI or second allo-SCT) provides the best results and should, whenever possible, be offered to patients with MDS who relapse after allo-SCT especially those with low tumor burden. Patients who received cytoreductive treatment alone (be it chemotherapy or DMA) had less satisfactory outcome. Our results emphasize the need to perform prospective protocols combining cytoreductive treatments and immunotherapy. Disclosures: No relevant conflicts of interest to declare.

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