Anabolic Steroids in Myelodysplastic Syndromes: A Systematic Review

Background Anabolic steroids, such as danazol, have been used for years in the treatment of myelodysplastic syndromes (MDS). Their successful use has been documented in aplastic anemia, hypoplastic MDS, and immune thrombocytopenia, among other hematologic conditions. In patients with low-risk MDS, available treatment options are limited. Danazol is frequently used to improve symptoms and modify the disease course; however, its efficacy and optimal dosing schedule are unclear. Methods We conducted a systematic review of the literature to identify studies that used anabolic steroids, including danazol, in the treatment of MDS. In accordance to guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under ID CRD42019121467. We included case series with more than 15 patients, observational studies (cohorts and case control), and randomized trials where anabolic steroids were used to treat MDS. Following PRISMA guidelines, 2 independent reviewers assessed the studies obtained through the search strategy. Discrepancies were resolved by a third reviewer. Due to the heterogeneity of the findings, no meta-analysis was performed. Results A total of 1000 studies were identified through our search. After removing duplicates and undergoing Level 1 screening by 2 reviewers, 69 full text articles were assessed. Thirteen studies were included in the final review as the other studies did not meet inclusion criteria. Of these, 3 were retrospective cohorts, 8 prospective cohorts, and 2 randomized trials. A total of 366 patients with MDS were exposed to anabolic steroids throughout the studies with diverse outcomes reported. FAB classification was used by most of the studies to categorize MDS, with one exception that used the 2008 WHO classification. Diagnoses included refractory anemia, refractory anemia with ring sideroblasts, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia. All but 2 studies used danazol as their intervention, with the exceptions using other anabolic steroids as well as danazol. Dosage varied across studies with the majority aiming for a dose of danazol 600mg daily. Patient characteristics and interventions are summarized in Table 1. The intervention was sustained for at least 1 month and up to 12 months across studies. Outcomes reported are diverse with positive and negative studies identified. Unfortunately, outcomes are not comparable due to the presence of different response definitions with different hematologic improvement cutoffs. Reports of response were highly variable, with studies showing 5 - 75% response rates depending on their study response definitions. Multiple studies reported a trend in platelet count improvement. Response duration was not specified by all studies and was highly variable across the reports. Response definitions and outcomes are shown in Table 2. No significant adverse effects to danazol were reported in any of the studies reviewed. No specific analysis of benefit throughout the different MDS groups was reported in any of the studies. Conclusion Our systematic review highlights the significant lack of data and irregular results across studies. The heterogeneity of included populations, MDS classification, response criteria, and interventions, do not allow for evidence based recommendations regarding the use of danazol or anabolic steroids in MDS patients. Given the limited treatment options for low-risk MDS patients, particularly in low and middle income countries, further well designed studies are needed. Disclosures No relevant conflicts of interest to declare.

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DNA instability in low-risk myelodysplastic syndromes: refractory anemia with or without ring sideroblasts

Human Molecular Genetics ◽

10.1093/hmg/ddn113 ◽

2008 ◽

Vol 17 (14) ◽

pp. 2144-2149 ◽

Cited By ~ 10

Author(s):

B. Novotna ◽

R. Neuwirtova ◽

M. Siskova ◽

Y. Bagryantseva

Keyword(s):

Myelodysplastic Syndromes ◽

Low Risk ◽

Refractory Anemia ◽

Dna Instability ◽

Ring Sideroblasts

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Anabolic steroids in myelodysplastic syndromes: A systematic review

Leukemia Research ◽

10.1016/j.leukres.2020.106370 ◽

2020 ◽

Vol 94 ◽

pp. 106370

Author(s):

Alejandro Garcia-Horton ◽

Yashoda Valliere ◽

Alejandro Lazo-Langner

Keyword(s):

Systematic Review ◽

Myelodysplastic Syndromes ◽

Anabolic Steroids

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Myelodysplastic Syndrome: A Study of VA Population.

Blood ◽

10.1182/blood.v110.11.2470.2470 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2470-2470 ◽

Cited By ~ 2

Author(s):

Gina M. Matacia-Murphy ◽

Najla H. Al Ali ◽

Jeffrey A. Schrager ◽

M.S. Beg ◽

Malek M. Safa ◽

...

Keyword(s):

Overall Survival ◽

Treatment Options ◽

Large Population ◽

Case Series ◽

The United States ◽

Refractory Anemia ◽

Categorical Variables ◽

P Value ◽

Medical Centers ◽

Seer Data

Abstract Background: Epidemiology and outcome of myelodysplastic syndromes (MDS) in the United States is not well recognized. MDS became reportable to the Surveillance, Epidemiology, and End Results program (SEER) in 2001. Only one study is published examining the SEER data between 2001–2003 on MDS incidence, epidemiology and outcome. We report first study of MDS among large population in the Veteran Affair system. Methods: There are approximately 127 VA Medical Centers diagnosing and/or treating Cancer patients. The data collected by the medical centers cancer registries is aggregated as the VA Central Cancer Registry (VACCR) and is maintained by the Chief Program Office for Oncology at VA in Washington DC. We used the VACCR to analyze VA patients with MDS diagnosed between 1995 and 2005. The data was downloaded from the database using ICD-03 histology codes for MDS. Data was entered and analyzed using bio-statistical software SPSS. Kaplan-Meier curves were used for estimates of overall survival, chi square for comparison of categorical variables and t-test for continuous variables. Results: Between 1995 and 2005, 1411 MDS cases were registered in the VACCR database. The median age was 75 years. Among those 1379 (97.7%) were males and 1196 (84.4%) were white patients, 171 (12.1%) black, and 44 (3.5%) other race. Majority of cases were reported as MDS, NOS 935 (66.3%), Refractory anemia (RA) 180 (12.8%), Refractory anemia with ring sideroblasts (RARS) 105 (7.4%), Refractory anemia with multilineage dysplasia (RCMD) 22 (1.6%), 5 q syndrome 13 (0.9%), Refractory anemia with excess blasts (RAEB) 105 (7.4%), Refractory anemia with excess blast in transformation 17 (1.2%), and therapy related MDS (t-MDS) 34 (2.4%). No IPSS data were available. The median overall survival (OS) was 1.8 year (95% CI 1.5–2.1). The 3 year and 5 year overall survival was 30% and 22% respectively. The median OS for RA patients was 3.7 year, RARS 4.9 year and for RAEB was 0.8 year. No difference was observed in OS between whites and black (median OS 1.73 versus 2.65, p value 0.28). Their was a non statistically significant trend for improvement of OS in patients diagnosed in 2004–2005 compared to 1995–2003 (time where azacitidine and lenalidomide were approved) median OS of 3.2 versus 1.8 (p value 0.64). Conclusion: This is the first report of MDS case series in the VA system. Outcome is similar to what is described in literature and SEER data (3 Year OS was 30% in our VA population study compared to 35% in recently published SEER data). No racial disparities are observed in outcome. A trend towards better overall survival is noted in the last 2 years since approval of new treatment options. Coding for WHO subtypes, IPSS and treatment options should be considered in all large MDS registries.

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A Randomized Phase IIa Study of Vorinostat in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes: Preliminary Results

Blood ◽

10.1182/blood.v112.11.5084.5084 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5084-5084 ◽

Cited By ~ 3

Author(s):

Guillermo Garcia-Manero ◽

Lewis B. Silverman ◽

Ivana Gojo ◽

Laura Michaelis ◽

Simrit Parmar ◽

...

Keyword(s):

Adverse Events ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Treatment Options ◽

Low Risk ◽

Red Blood Cell Transfusion ◽

Study Medication ◽

Cutaneous Manifestations ◽

Preliminary Results ◽

Transformed Cell Lines

Abstract Effective treatment options for patients with lower-risk myelodysplastic syndromes (MDS) are limited. However, around one-third of patients experience transformation to acute myeloid leukemia, and absent transformation, complications of chronic cytopenias (including infection), and iron-overload syndromes can be fatal. Although 5-azacitidine, decitabine, and lenalidomide have improved treatment options for patients with MDS, these are not routinely used in patients with lower-risk disease. Histone deacetylase (HDAC) enzymes are overexpressed in several tumor types including MDS, and regulate transcriptional and post-transcriptional processes. Vorinostat (Zolinza®) has been shown to inhibit class I and II HDAC enzymes, and has been approved by the FDA for the treatment of cutaneous manifestations of T-cell lymphoma in patients with persistent or recurrent disease, on or following 2 prior systemic therapies. Vorinostat induces cell-cycle arrest, apoptosis, or differentiation in a variety of cultured transformed cell lines, and has demonstrated activity against leukemias in in vivo non-clinical models and in phase I and II clinical trials. Efficacy data in these early phase trials prompted an investigation of vorinostat monotherapy in lower-risk MDS. The potency and tolerability of vorinostat suggest it may be effective in the treatment of MDS. Here, we report preliminary results of a randomized phase II study evaluating once-daily and three-times-daily (tid) intermittent dosing schedules of vorinostat in patients with low and intermediate-1 risk MDS. Primary objectives included assessment of the efficacy, safety, and tolerability of vorinostat. Eligible patients were aged ≥18 years, had either previously untreated disease, or were ≥4 weeks from any prior treatment regimen (including growth factors). Patients’ performance status was ≤2 on the ECOG performance scale, they had adequate organ function, and were either red blood cell transfusion dependent or had a hemoglobin level of ≤11g/dL at the time of screening, or had platelets ≤100 × 109/L at the time of screening. Eligible patients were assigned to 1 of 2 oral dosing regimens: vorinostat 400 mg daily or vorinostat 200 mg tid. Treatment was administered over a 21-day cycle (14 days’ therapy and 7 days’ rest), with patients receiving up to 8 cycles, or until the patient experienced unacceptable toxicity, disease progression, or withdrew consent. In total, 18 patients (12 male, 6 female; mean age 67.4 years) have been randomized, including 5 with low-risk MDS and 13 with intermediate-1 risk MDS, as defined by the International Prognostic Scoring System. Of the patients enrolled, 12 (3 low-risk and 9 intermediate-1 risk MDS) were evaluable for response and have received between 2 and 6 cycles of treatment. Stable disease has been reported in all 12 patients, with a reported duration of between 22–146 days (low-risk MDS) and 1–136 days (intermediate-1 risk MDS). A total of 11/18 (61%) patients have discontinued, 2 due to adverse events (1 event of grade 4 neutropenia [unrelated to study medication] and 1 event of grade 3 neuropathy [drug related]), 1 due to deviation from protocol, 4 due to lack of efficacy, 3 due to physician decision, 1 due to progressive disease, and 1 because of withdrawal of consent. Most adverse events were gastrointestinal disorders: diarrhea in 10 patients (7 grade 1, 3 grade 2), nausea in 9 patients (6 grade 1, 3 grade 2), and vomiting in 6 patients (5 grade 1, 1 grade 2). Grade 4 neutropenia, anemia, and thrombocytopenia were observed in 2, 1, and 1 patients, respectively; however these were unrelated to study medication. Data from this study indicate that vorinostat administered in a 21-day cycle has acceptable safety and tolerability.

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Clinical and Biological EFFECTS of 5-Azacitidine FIVE Days/Monthly Schedule IN Symptomatic LOW-RISK (IPSS: 0-1) Myelodisplastic Patient.

Blood ◽

10.1182/blood.v114.22.4851.4851 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4851-4851

Author(s):

Carla Filí ◽

Marco Gobbi ◽

Giovanni Martinelli ◽

Carlo Finelli ◽

Ilaria Iacobucci ◽

...

Keyword(s):

Conflicts Of Interest ◽

Biological Effects ◽

Treatment Plan ◽

Low Risk ◽

Refractory Anemia ◽

Hematologic Toxicity ◽

Polymorphism Analysis ◽

Cytokine Network ◽

Who Grade ◽

Biological Studies

Abstract Abstract 4851 Background Nucleoside 5-Azacitidine (5-Aza) administered at a dose of 75mg/mq/day subcutaneously for 7 days, every 28 days, induces high hematologic response rates, reduces progression to acute myeloid leukaemia (AML) and increases overall survival in the high risk MDS patients. Aim The use of 5-Aza in the earlier phases of MDS could reduce the proliferative advantage of MDS clone and favours the regrowth of normal hematopoiesis. In the setting of low-risk MDS patients lower doses of 5-Aza could be enough to induce hematologic responses. We attempted to use an alternative schedule, 75 mg/mq subcutaneous daily for 5 consecutive days every 28 days, for a total of 8 courses, to evaluate its efficacy and tolerability in low risk MDS patients. Pharmacogenomic studies (gene expression profile and single nucleotide polymorphism analysis), cytokine network and phosphatidylinositol-phospholipase C – β1 (PI-PLC - β1) expression, before and after 5-Aza treatment, were planned to identify new biological markers to predict the response. Methods From September 2008 to August 2009, 25 patients were enrolled into the study. According to WHO criteria 12 patients had refractory anemia (RA), 5 patients refractory cytopenia with multilineage dysplasia (RCMD), 7 patients refractory anemia with excess blasts-1 (RAEB-1) and 1 patient refractory anemia with ringed sideroblasts (RARS). All patients were classified as Low Risk (IPSS score 0-1). Age at diagnosis ranged between 56 and 84 years. All patients failed previously EPO therapy and were in chronic red blood cell (RBC) supportive care with a median transfusions requirement of 4 units/monthly. The response treatment criteria was according to IWG 2006. Results 9/25 (36%) patients completed at least 4 courses of therapy and only 6/25 (24%) patients finished the treatment plan (8 courses). Five patients obtained an hematologic improvement (3 erythroid response and 2 neutrophil response) whereas 4 patients maintained a stable disease. The others 16 patients are ongoing. The drug was very well tolerated. WHO grade III hematologic toxicity consisted in neutropenia (1 case) and thrombocytopenia (1 case) was observed in only two patients, but it was transitory and no delay of treatment was necessary. Conclusion Our preliminary results show that the 5-Aza five days/monthly schedule is very well tolerated and it appears to induce hematologic improvements as well as the seven days/monthly schedule, at least in the low-risk MDS setting. Biological studies will be useful to elucidate the genetic bases of sensititvity or resistance to 5-AZA and to optimise the therapy.Acknowledgments: this work was supported by MIUR 2008. Disclosures No relevant conflicts of interest to declare.

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Retrospective Analysis of Patients with Refractory Cytopenia with Unilineage Dysplasia.

Blood ◽

10.1182/blood.v114.22.4847.4847 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4847-4847

Author(s):

Yuchun Wang ◽

Xin Du ◽

Suxia Geng

Keyword(s):

Myelodysplastic Syndromes ◽

Who Classification ◽

Conflicts Of Interest ◽

Major Change ◽

Classification Systems ◽

World Health ◽

Refractory Anemia ◽

Prognostic Information ◽

Prognostic Assessment ◽

Health Organization

Abstract Abstract 4847 Background Myelodysplastic syndromes (MDS) are a group of clonal heterogeneous bone marrow stem cell disorders characterized by dysplastic hypercellular marrows with peripheral cytopenias. Accurate diagnosis and classification are essential for subgroup identification and prognostic assessment of patients with MDS. Classification systems such as the World Health Organization (WHO) classification are widely used but do not always provide sufficient prognostic information. So WHO improved the classification systems last year(2008). The major change was that refractory anemia (RA) was substituted by refractory cytopenia with unilineage dysplasia (RCUD). The aim of this study was to apply the new WHO classification to re-evaluate MDS with RA. Methods MDS patients with RA diagnosed between 2000 and 2008 were retrospectively reclassified with WHO criteria (2008). Results According to the new WHO classification, RCUD is intended to encompass those myelodysplastic syndromes (MDS) which present with a refractory cytopenia with unilineage dysplasia and includes refractory anemia (RA), refractory neutropenia (RN) and refractory thrombocytopenia (RT), so in 34 cases diagnosed as RA, 12 cases (12/34,35%) still pertained to RA, 19 cases (56% ) to RN and 3 (9%) cases to RT. IPSS showed 94% of RCUD cases categorized as low or intermediate-I risk. The median survival of patients with RCUD was 84 months. Conclusions RA is the main subtypes of RCUD. Understanding the clinical features of RCUD accurately is helpful to determine the right subtype of RCUD. The new WHO classification system was improved to provide better diagnostic criteria. Disclosures No relevant conflicts of interest to declare.

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Cytogenetic Analysis in Patients with Newly Diagnosed Myelodysplastic Syndromes in Southern Italy

Blood ◽

10.1182/blood.v120.21.50623.50623 ◽

2012 ◽

Vol 120 (21) ◽

pp. 50623-50623

Author(s):

Esther Natalie Oliva ◽

Francesco Albano ◽

Nicola Di Renzo ◽

Vincenzo Pavone ◽

Stefano Molica ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndromes ◽

Cytogenetic Analysis ◽

Southern Italy ◽

Conflicts Of Interest ◽

Refractory Anemia ◽

Newly Diagnosed ◽

Conventional Cytogenetic Analysis ◽

Conventional Analysis ◽

Italian Regions

Abstract Abstract 50623 Background: Bone marrow karyotype in myelodysplastic syndromes (MDS) is essential to define the prognosis and to guide treatment decisions, including targeted therapies. Due to the lack of an extensive national MDS registry in Italy, epidemiological data on MDS, including cytogenetics, throughout the territory is unknown. Objective: We evaluated the incidence of cytogenetic abnormalities amongst newly diagnosed MDS patients in in 2 southern Italian regions (Calabria and Puglia). Methods: A pilot project, denominated ANDROMEDA (ANalysis of cytOgenetics alteRatiOn in the MyEloDysplAstic syndromes) was developed in 17 centers to offer a service of conventional cytogenetic analysis for all consecutive patients undergoing diagnostic evaluation for cytopenia and suspected MDS between January 1 and December 31, 2011. The study conformed to the ethical standards set out in the Declaration of Helsinki and was approved by institutional review boards at each participating center. Patients were required to provide their written informed consent. Clinical characteristics of patients and bone marrow morphology, iron staining and histology were registered. Bone marrow samples were centralized for standard cytogenetic studies and fluorescence in situ hybridization to two dedicated genetics laboratories (one for each region), blind to patients' data. Results: Two hundred and thirty-five patients were evaluated and MDS diagnosis was confirmed in 220 cases (88. 3%), according to WHO criteria. The overall incidence of clonal chromosome abnormalities detected by conventional analysis was 36. 9%. Single abnormalities included +8 (13 cases, 5. 8%), del(5q) (12 cases, 5. 4%), –Y (11 cases, 5. 0%) and del(7)/-7 (4 cases, 1. 8%). Complex karyotypes were detected in 18 (8. 1%) cases. Among all cases only 10 (4. 5%) bone marrow samples were not evaluable for cytogenetic analysis. FISH revealed additional abnormalities not identified by conventional analysis only in 3 (1. 3%) out of 72 cases. Patients were classified in WHO subtypes: 39. 2% refractory cytopenia with unilineage dysplasia (RCUD), 1. 5% refractory anemia with ring sideroblasts (RARS), 32. 5% refractory cytopenia with multilineage (RCMD), 10. 8% refractory anemia with excess of blast-1 (RAEB-1), 9. 3% refractory anemia with excess of blast-2 (RAEB-2), 4. 1% MDS with deletion 5q (MDS 5q-) and 2. 6% MDS unclassifiable (MDS-U). Conclusions: These preliminary results demonstrate that the incidence of abnormal karyotype patterns and WHO subgroups in MDS patients in Southern Italy is comparable with that described in other geographical areas. It is confirmed that conventional cytogenetic analysis is a standard in the diagnostic workup of MDS of patients with a suspected myeloid malignancy in order to identify primary abnormalities and prognostic models. Disclosures: No relevant conflicts of interest to declare.

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Breast Implant Related Anaplastic Large Cell Lymphoma ALK- (ALCL ALK-) – Case Report

Blood ◽

10.1182/blood.v122.21.5086.5086 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5086-5086 ◽

Cited By ~ 3

Author(s):

Alejandro Arbelaez ◽

Laurence Catley ◽

Louis Pool

Keyword(s):

Conflicts Of Interest ◽

Case Reports ◽

Breast Implant ◽

Treatment Options ◽

Fluid Collection ◽

Case Series ◽

Breast Implants ◽

Large Cell ◽

Lymphoid Cells ◽

Malignant Cells

Abstract Case presentation A 29 underwent bilateral cosmetic breast augmentation 10 years previously (McGhan Textured Round 400 mL implants). Six months before, she developed slowly progressive right breast pain and inflammatory signs associated with fluid collection around the right breast that was drained. A yellow cloudy fluid was examined and showed atypical large lymphoid cells. The cell block prepared in another institution showed numerous lymphoid cells including large atypical cells with lobated nuclei. PET CT scan was negative, same as bone marrow aspirate and trephine for lymphoma infiltration. Following bilateral removal of the breast implants, further histopathology studies showed no infiltration by lymphoma of the breast capsules or scar tissue. However, right breast peri prosthetic fluid microscopy showed a population of single malignant cells with scanty cytoplasm, numerous mitosis, and nuclei showing single and multiple nucleoli. Some cells showing horseshoe nuclei. The malignant cells were positive for CD30 and LCA and negative for CD20, CD68, AE1-3, and ALK 1. FISH for ALK was not possible (Fig 1) Discussion Primary breast lymphomas are very rare conditions; they represent less than 1% of all NHL and less than 0.7% of all breast malignancies. There have been some cases reported in the medical literature of ALCL ALK- associated with breast implants. All the cases have been described in patients with textured implants, such as in this case and the reason is unknown. There are two main types of ALCL of the breast based on published case reports: a mass and an effusion. Primary breast effusion associated ALCL portends a good prognosis despite the fact that they are ALK-. The development of ALCL proximal to breast implants suggests that they are the result of an immune reaction to the silicone. Whether they represent true malignancy or a localised reactive phenomenon is not entirely clear yet. In previous case series, the condition has been described as indolent. However, given the low incidence of this condition and the limited literature available; it is difficult to know what the best treatment approach is. Following confirmation of the diagnosis, treatment options were discussed with the patient and the preferred option was active treatment with local radiation after removal of breast implants. Disclosures: No relevant conflicts of interest to declare.

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Sustained Erythroid Response Associated With Red Cell Transfusion and Progressive Growth Factor Independence Is Feasible With Adjuvant Sertraline In Low-Risk Myelodysplastic Syndrome (LR-MDS)

Blood ◽

10.1182/blood.v122.21.5235.5235 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5235-5235

Author(s):

Rui Li ◽

Matthew Zheng ◽

Sarvari Venkata Yellapragada ◽

Ruben Hernandez Perez ◽

Martha Mims ◽

...

Keyword(s):

Growth Factor ◽

Selective Serotonin Reuptake Inhibitors ◽

Conflicts Of Interest ◽

Treatment Algorithm ◽

Low Risk ◽

Refractory Anemia ◽

Cytokine Signaling ◽

Absolute Increase ◽

Erythroid Response ◽

Tnf Α

Abstract Background LR-MDS is a heterogeneous group of clonal marrow disorder associated with ineffective hematopoeisis and complex genomic etiology. For patients (pt) with refractory cytopenia phenotype (RC-P), transfusion and growth factor support, such as Erythropoietin Stimulating Agents (ESAs) and Granulocyte Colony Stimulating Factor (G-CSF), are treatment options. Response rates for ESA is about 30%, (and response potentiation can be achieved in about 35% of pt receiving concurrent G-CSF.However, ESA unresponsiveness is a common phenomenon and is associated with transfusion dependence, normal/high EPO levels, and high IPSS score. Therefore, novel therapies are greatly needed. Biologically, LR-MDS is linked to deregulation of apoptosis and cytokine signaling pathways. Selective Serotonin Reuptake Inhibitors (SSRIs) can induce normalization of deranged cytokines such as IL6 and TNF-α in clinical depression. In animal model of arthritis, sertraline abrogates manifestation of autoimmune arthritis by reducing TNF α. Our group recently showed that significant improvement in overall survival (OS) can be achieved in low-risk MDS patients treated with SSRIs, such as sertraline, which is independent of concurrent MDS directed therapy. (Li, et al. ASH 2012 abstract # 3818) Here, we report a case of sequential reversal of transfusion and growth factor dependence phenotype in a pt with refractory anemia multi-lineage dysplasia LR- MDS. Methods A 72-year male with transfusion dependent refractory anemia (8 units RBC in 8 weeks) was evaluated in clinic. His bone marrow showed erythroid and megakaryocytic dysplasia consistent with RCMD by WHO 2008 classification. Cytogenetic study revealed 45;X-Y[4];46 XY[16]. R-IPSS=1.5 (Cytogenetic=0; blast [0%] =0; Hb=7g/dL=1.5; Platelets [135000] =0; ANC [1500] =0). EPO and ferritin levels were 449 IU/L and 1600 NG/ML, respectively. R-H-EPO was administered at 40000 IU subcutaneously (SQ) per week. In view of severe depression, pt initiated sertraline at 100 mg orally on day (D) 61 of treatment. Response after 12 weeks of ESA, sequential addition of G-CSF and sertraline, were assessed according to internal working group (IWG) 2006 criteria. Results After 3 months of standard weekly SQ ESA (D1-D92) (Fig.1), and given ESA refractoriness, G-CSF at 480 mcg SQ 5-times weekly was added (ESA + G-CSF schedule) (D92-D189).Transfusion independence was observed by D 161 of combined ESA+G-CSF(Fig.1). Progressive hemoglobin stabilization resulted in G-CSF dose reduction to twice a week from D189 –D 257 (Fig. 1). Sequential resolution of ESA dependence was observed from D257- D515. Over the treatment period, the absolute increase in Hb level was 4.2 g/dL from baseline. Restoration of ESA erythroid response was observed by D93-210 after G-CSF and sertraline addition. (Table. 1) Sustained and improved Hb levels were achieved after 200 days of G-CSF discontinuation and ESA dose de-escalation while on sertraline treatment. Conclusions Reversal of transfusion dependence represents a critical step in treatment algorithm of LR-MDS pt presenting with refractory anemia. In this context, ferritin normalization has previously been recognized as independent prognostic factor for outcome in MDS. Our case suggests feasibility of restoration of ESA sensitivity with concurrent G-CSF+ sertraline, and evidence for sustained beneficial effect of sertraline while ESA de-escalation, which seems independent from G-CSF. The MDS disease modifying effect of sertraline in LR- MDS patient presenting with refractory anemia and experiencing ESA refractoriness should be evaluated in prospective trials. Disclosures: No relevant conflicts of interest to declare.

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A systematic review on conservative and non-operative treatment options for Osgood-Schlatter disease

10.31236/osf.io/u4vn7 ◽

2020 ◽

Author(s):

Cornelia Neuhaus ◽

Christian Appenzeller-Herzog ◽

Oliver Faude

Keyword(s):

Systematic Review ◽

Operative Treatment ◽

Treatment Options ◽

Grey Literature ◽

Case Series ◽

Outcome Data ◽

Control Group ◽

Retrospective Case ◽

Review Articles ◽

Knee Pathology

Background: Osgood-Schlatter disease (OSD) is a sport- and growth-associated knee pathology with painful osteochondrosis around the tibial tuberosity. Up to 10% of adolescents are affected by OSD. Treatment is primarily conservative or non-operative and includes injections, ice, braces, casts, tape and/or physiotherapy. However, treatment outcomes are often insufficiently described and there is lack of evidence for current best practice.Objective: The aims of this systematic review are to comprehensively identify conservative or non-operative treatment options for OSD, to compare their effectiveness in selected outcomes, and to describe potential research gaps. and to describe potential research gaps.Methods: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. CENTRAL, CINAHL, EMBASE and MEDLINE via Ovid, and PEDro were searched through to January 6, 2020. In addition, ongoing and unpublished clinical studies, dissertations, and other grey literature on OSD were retrieved. We included prospective, retrospective, case control, randomised, and non-randomised studies reporting on the effectiveness of any conservative or non-operative treatment of 6- to 28-year-old OSD patients. Studies written in English, German, or French were included. The quality of the included studies was assessed using the PEDro scale and extracted outcome data were narratively synthesized. In addition, we also systematically retrieved review articles for extraction of treatment recommendations.Results: Of 767 identified studies, thirteen were included: two randomised controlled trials (RCTs), two prospective and eight retrospective observational studies, and one case series. Eight studies had no control group. The included studies were published from 1948 to 2019 and included 747 patients (563 male, 119 female, 65 sex not reported) with 937 affected knees. The study quality was poor to moderate. The two included RCTs examined the effectiveness of surplus dextrose-injection in OSD patients treated with local anaesthetics injection and came to opposite conclusions. Other than that, inter-study heterogeneity prohibited any descriptive cumulative analyses. Among the 15 review articles, the most prevalent treatment recommendations were activity modification (15/15), quadriceps and hamstring stretching (13/15), medication (11/15), ice (11/15), strengthening of the quadriceps (9/15), and knee straps or brace (8/15).Conclusion: Conflicting evidence exists to support the use of dextrose injections. Certain therapeutic approaches, such as stretching, seem to work, but no RCT comparing specific exercises with sham or usual care treatment exists. Carefully controlled studies on well- described treatment approaches are needed to establish which conservative or non-operative treatment options are most effective for patients with OSD.

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