Late Relapsing Multiple Myeloma ≥ 10 Years after Treatment on Total Therapy Protocols Are Associated with Good Outcome

Introduction Novel agents are incorporated into a backbone of multi-agent chemotherapy and tandem transplantation in successive Total Therapy (TT) protocols for multiple myeloma (MM) patients. The TT protocols extend the duration of remission with a significant proportion of patients achieving long-term disease control. However, a small percentage of patients have documented late relapse and we theorize that these relapses are indolent with overall good clinical outcome. While even a late relapse is seemingly an undesirable outcome, defining the clinical implications is imperative to understanding the impact on long-term prognosis and management. Methods Our MM database was interrogated to identify patients that presented with relapsing disease ≥ 10 years from diagnosis and were treated on TT protocols. All patients had myeloma markers every 2 to 3 months and bone marrows with either PET-CT or MRI at least once a year. In the group of patients with documented relapse, we obtained the pattern of relapse, clinical and laboratory markers, cytogenetics, FISH, gene expression profile (GEP), bone marrow (BM) minimal residual disease (MRD), imaging (PET-CT and MRI, use of salvage transplant, and response assessment including best response to treatment. Patterns of relapses were evaluated based on elevated serum myeloma markers, BM plasmacytosis and presence of macrofocal relapse/extramedullary disease. Clinical relapses were classified based on the International Myeloma Working Group criteria. Indolent relapse was defined as a biochemical relapse with a rising M-protein or free light chains, less than 30% bone marrow plasmacytosis involvement, absence of focal lesion on imaging and of CRAB criteria, low riskGEP70 signature at relapse or no abnormal metaphase cytogenetics. Results A total of 2055 patients were enrolled and treated on successive TT protocols (TT1 to TT7) of which 658 patients had ≥10 years follow up from initial study enrollment. Among these 658 patients, 8% (53/658) had a clinical relapse ≥ 10 years from diagnosis. The median time to clinical relapse was 11. 8 years (range, 9.8 - 17.6). Median age at the time of relapse was 67.7 years with 28% being females. Gene expression profiling showed that 45% (24/53) belonged to the molecular CD2 and LB subgroups. The most common pattern of relapse is with BM plasmacytosis in 49% (26/53) with 36% (19/53) presenting with CRAB clinical features. Focal lesions by MRI and/or CT-PET were present in 35.8% (19/53). Overall, 56.6% (30/53) of patients had indolent relapses; of these 9 and 7 belonged to the CD2 and LB molecular subgroups, respectively. BM MRD assessment by 8-color flow cytometry was available in 17 patients and MRD positivity preceded clinical relapse by a median 17.9 months (range: 0 - 60.8). Forty-one patients required treatment for disease relapse with 11 patients managed expectantly without treatment. While most patients (73.1%, 30/41) received initial treatment with either PI/IMiD/PI IMiD combinations, 8 patients later underwent salvage ASCT. A response of ≥ VGPR was attained in 70% (31/47) of the treated patients with the large majority (87%) achieving a sCR/CR. The overall survival from relapse at 5 years was 73.3% (95% CI: 55.0% to 85.1%). A total of 14/53 patients died during follow-up;7 patients died to progressive disease; 6 of these 7 presented with focal lesions detected on imaging and had an aggressive relapse. Three patients died to treatment related complications, 1 had an unrelated pneumonia, the cause of death was indeterminate in 2 and unknown in 1. Overall, in these 14 patients, median time to death from initial diagnosis was 15.4 years (range: 11.8 - 18.0) and a median time to death from relapse was 3.2 years (range: 0.3 - 6.0). Conclusions Late relapses (>10 years) in MM are a rare event occurring in 8% of long-term survivors and accounting for 2.6% of all patients treated on the TT protocols. Intriguingly, most patients with late relapsing MM belong to the GEP subtype LB and CD2 and accounted for 51% of the indolent relapses. These findings have clinical implications and emphasizes the importance of extended and close follow-up even in patients with prolonged clinical remission. Disclosures van Rhee: Karyopharm: Consultancy; Adaptive Biotech: Consultancy; Takeda: Consultancy; EUSA: Consultancy; CDCN: Consultancy.

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Clinical implications of loss of minimal residual disease (MRD) negativity in multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.8514 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 8514-8514

Author(s):

Meera Mohan ◽

naveen kumar yarlagadda ◽

Dinesh Atwal ◽

Yadav Pandey ◽

Arya Roy ◽

...

Keyword(s):

Multiple Myeloma ◽

Median Time ◽

Plasma Cells ◽

Residual Disease ◽

Significant Proportion ◽

Clinical Relapse ◽

Long Term Follow Up ◽

Highly Correlated

8514 Background: Attainment of MRD negativity in multiple myeloma (MM) patients is increasingly considered an optimal therapeutic endpoint, but little is known about the MRD evolution in those who achieve this milestone. We investigated the clinical implication of loss of MRD negativity or MRD conversion in patients with ≥VGPR. Methods: We identified and followed 606 patients achieving a sustained ≥VGPR with bone marrow MRD negativity(≥ 2 consecutive reading) following treatment on a total therapy protocol and with a median follow-up of 10 y. All patient had negative PET and MRI DWIBS at enrollment. Serial BM aspirate MRD was determined by 8-color next generation flow (NGF, EuroFlow) with a minimal sensitivity of 10−5 cells. Results: Most MM patients were considered low risk with a UAMS GEP70 score of ≤ 0.66 (92%; 495/538) . While 60% (364/606) of patients had sustained MRD negativity, the remaining 40% (242/606) experienced MRD conversion with a 5.7 y median time from ASCT and 6.3 y from diagnosis. The risk of clinical relapse was significantly elevated in patients with MRD conversion compared to sustained MRD negativity (73%, 177/242 vs. 5%, 18/364; R.R. = 3.5; P< 0.0001). The median level of MRD positivity (> 0.2 ratio of MM cells to normal plasma cells) also highly correlated with relapse ( P< 0.0001). Loss of MRD negativity preceded clinical relapse by a median time of 1.1 years. Loss of MRD negativity without clinical relapse was seen in 27% (65/242). MRD conversion was associated with an inferior PFS and OS (PFS: 10.2 y vs. NR; P < 0.0001, H.R. 18.7; 95% CI 13.3 - 26.3 and OS: 26.1 y vs. NR; P= 0.01, H.R. 1.7; 95% CI 1.1 - 2.6). Furthermore, when MRD conversion was within 5 y of diagnosis compared > 5 y, patients had a worse OS ( P < 0.0001, H.R. 17.2; 95% CI 7.8 – 37.8). We also observed that MRD conversion later than 5 years from diagnosis did not affect the OS. In a subset of patients (n = 144) the timing of first MRD negativity following treatment was available. Attainment of MRD negativity within 6 months of diagnosis compared to any time after 6 months was predictive of future MRD conversion (65%, 17/26 vs.42%, 49/118; P = 0.03) and clinical relapse (54%, 14/26 vs.28%, 33/118; P = 0.02). Conclusions: MRD conversion occurs in a significant proportion of MM patients (40%) on long-term follow-up and predicts future clinical relapse. Significance of MRD conversion has a temporal relationship from diagnosis and portray inferior clinical outcome particularly within 5 years of diagnosis.

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Long-Term Outcomes of Chronic Myeloid Leukemia Patients Who Lost Undetectable Molecular Residual Disease (UMRD) after Imatinib Discontinuation: Korean Imatinib Discontinuation Study (KIDS)

Blood ◽

10.1182/blood-2019-126376 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1643-1643 ◽

Cited By ~ 1

Author(s):

Sung-Eun Lee ◽

Joon Seong Park ◽

Hyeoung-Joon Kim ◽

Sung-Hyun Kim ◽

Dae Young Zang ◽

...

Keyword(s):

Median Time ◽

Research Funding ◽

Residual Disease ◽

The Other ◽

Risk Scores ◽

Late Relapse ◽

Molecular Response ◽

Long Term Follow Up

Background The recent discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation. Moreover, treatment rechallenge in patients with molecular recurrence lead a second deep molecular response, suggesting that IM discontinuation is safe. However, the issues on the definition of molecular relapse requiring treatment resumption and the occurrence of late relapse with a long-term follow-up after IM discontinuation are important. Therefore, here we analyzed the long-term follow-up results of the patients who lost UMRD after IM discontinuation Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18-82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32-141) and 41 months (range, 22-131), respectively. After a median follow-up of 62.6 months (range, 4.9-100.8 months) after IM discontinuation, 83 patients (65.9%) lost UMRD. Among them, 56 (67.5%) patients lost MMR in 2 consecutive analyses. The other 27 (32.5%) patients who lost UMRD but not MMR exhibited different patterns of BCR-ABL1 kinetics: 8 patients spontaneously re-achieved UMRD after a median time of 2.8 months (range, 0.9-3.0 months), and 19 patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for a median 19 months (range, 3-34), and then spontaneously returned and maintained UMRD for a median 31 months (range, 2-64). Of 73 patients who lost MR4.0, the rate of MMR loss was 76.7%. Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died. Another patient lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but progressed to AP on the assessment 32 months later. The patient switched to dasatinib and lost follow-up. Among the patients who maintained a second UMRD for at least 2 years after IM resumption, 23 patients entered into a second IM stop. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusions Our results showed that 67.5% and 76.7% of patients who lost UMRD and MR4.0, respectively resulted in MMR loss, and the other patients were below MMR without re-treatment, suggesting loss of MMR can be chosen for treatment re-challenge. Overall, IM discontinuation could be applied with approximately 55% of probability of sustained MMR in the long term. In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted. Disclosures Kim: Il-Yang co.: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; BMS: Research Funding; Novartis: Research Funding.

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Low-Dose 28-Day Metronomically Scheduled Therapy (METRO) for Newly Diagnosed High-Risk Multiple Myeloma: A Pilot Study

Blood ◽

10.1182/blood.v124.21.5770.5770 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5770-5770

Author(s):

Rashid Z Khan ◽

Yogesh Jethava ◽

Xenofon Papanikolaou ◽

Caleb K Stein ◽

Adam Rosenthal ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Focal Lesions ◽

Advisory Committees ◽

Pet Ct ◽

Metronomic Therapy ◽

Total Therapy

Abstract Introduction: Gene expression profiling (GEP)-defined high-risk de novo multiple myeloma (HI-MM) has a dismal prognosis with median PFS and OS stagnating at 2 and 3 years, respectively, despite the incorporation of novel agents into our Total Therapy (TT) trials. Having seen encouraging results in relapsed-refractory MM with an extended 16-day metronomic therapy (Papanikolaou, Haematologica 2014), we tested this approach in a small cohort of untreated patients with HI-MM. METRO emphasizes targeting neo-angiogenesis and other components of the bone marrow micro-environment while avoiding cytokine surges with recovering hematopoiesis following myelotoxic therapy. Patients and Methods: 10 previously untreated patients with HI-MM, who were either ineligible or unwilling for our Total Therapy protocols received a single cycle of METRO. Therapy comprised of SC bortezomib 1.0mg/m2 (0.8mg/m2 in case of grade >2 peripheral neuropathy) on days 1, 4, 7, 10, 13, 16, 19, 22, 25 and 28 schedule, PO dexamethasone 12mg (8mg in case of prior intolerance of higher dose or diabetes mellitus) on days 1 to 4, 7 to 10, 13 to 16, 19 to 22 and 25 to 28, PO Thalidomide 100mg (50mg in case of peripheral neuropathy grade >2) and continuous IV infusions of doxorubicin and cisplatin at 1.0mg/m2 daily for 28 days. Cisplatin was dose-reduced for Cr >2mg/dL and omitted for Cr >3mg/dL. Arsenic tri-oxide was given at a fixed dose of 0.01mg/kg on the days after bortezomib. Laboratory monitoring for response and toxicities were done on a Monday-Wednesday-Friday schedule. Maximal responses, based on current IMWG definitions, were measured within 30 days of completion of cycle 1, and at least monthly thereafter. KM curves were current as of 07/31/14. The Institutional Review Board granted permission for our retrospective data review, the results of which are presented here. Results: Patient characteristics included age >=65 in 8, 5 male, 5 female with ISS III in 5 patients. Metaphase cytogenetic abnormalities (CA) were detected in 7 patients. GEP70 based high risk MM was present in all 10 patients, and GEP proliferation (PR) subgroup was dominant in 8 out of 10 patients. All 10 patients achieved at least PR, including 3 qualifying for VGPR and 4 for CR. Bone Marrow responses were equally encouraging in that 8 of 10 patients qualified for complete morphologic negativity including 4 with no minimal residual disease (MRD) by 8-color flow cytometry. Of 8 patients with FDG-avid PET-CT focal lesions, 6 achieved PET-CT CR; all patients showed decreases in SUV-max and SUV-diff (background SUV). Number and/or apparent diffusion coefficient (ADC) mapping of focal lesions and background marrow on diffusion-weighted MRI improved in all 7 evaluable patients. GEP70 risk morphed from high risk to low risk in 3/4 evaluable patients. Pre and post serologic, urinary and radiologic responses are shown in Figure 1. The median follow-up time for the population was 3.2 months (98 days). All 10 patients are alive from 1 to 7 months, and 1 suffered progression (Figure 2). Overall tolerance was good. Non-hematologic grade 3/4 SEs included fatigue, electrolyte abnormalities (20%), dyspnea, hypotension, LE edema and transaminitis (10%). Conclusion: Primary 28-day metronomic therapy is highly effective and well-tolerated in patients with previously untreated HI-MM. Further prospective studies with longer follow-up are currently being devised in an attempt to improve outcomes in this population. Figure 1: Individual responses Figure 1:. Individual responses Figure 2 Figure 2. Figure 3 Figure 3. Disclosures van Rhee: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Zangari:Norvartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Research Funding; Millennium: Research Funding.

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Long-Term Follow-up after Treatment Discontinuation in Patients with Chronic Myeloid Leukemia: The Korean Imatinib Discontinuation (KID) Study

Blood ◽

10.1182/blood-2018-99-118026 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4252-4252 ◽

Cited By ~ 4

Author(s):

Dae Young Zang ◽

Won Sik Lee ◽

Yeung-Chul Mun ◽

Young Rok Do ◽

Sukjoong Oh ◽

...

Keyword(s):

Median Time ◽

Research Funding ◽

Residual Disease ◽

Blast Crisis ◽

Risk Scores ◽

Late Relapse ◽

Molecular Response ◽

Long Term Follow Up

Abstract Background With first-line imatinib (IM) therapy, approximately 50% of CP CML patients achieve undetectable molecular residual disease (UMRD). The recent several discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and UMRD durations prior to IM discontinuation. In our previous report, we have reported that of 90 patients with follow-up ≥12 months, the probability of sustained major molecular response (MMR) at 12 months and 24 months was 62.2% and 58.5%, respectively. However, currently, the issue on the occurrence of late relapse with a long-term follow-up after IM discontinuation is important. Therefore, here we analyzed the long-term follow-up results of the KID study. Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction for at least 2 years were eligible for KID study. After IM discontinuation, the molecular response was monitored using the following schedule: every month for the first 6 months, every 2 months up to 12 months, and every 3 months thereafter. In cases of MMR loss after 2 consecutive assessments (molecular relapse), IM treatment was re-introduced. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18 - 82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32 - 141) and 41 months (range, 22 - 131), respectively. After a median follow-up of 43 months (range, 4.9 - 93.6) after IM discontinuation, 55 patients lost MMR in 2 consecutive analyses at a median time of 3 months (range, 0.9 - 53.2 months). The 12-month and overall probability of sustained MMR was 61.9 ± 4.3% and 55.1 ± 4.6%, respectively. UMRD (P = 0.001) and IM duration on treatment (P = 0.003) were associated with the probability of sustained MMR. Out of 55 patients with molecular relapse, 53 patients (except 2 patients with follow-up loss) were re-treated with IM for a median of 31.7 months (range, 5.8 - 82.9 months), 51 patients re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming IM therapy and 48 of these patients re-achieved UMRD at a median of 5.8 months (range, 0.9 - 19.7 months). 2 patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient with 45.8 and 40.3 months of IM therapy duration and sustained UMRD duration prior to discontinuation, respectively lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but MMR was lost again on the assessment 8 months later. Another patient with 122.2 and 30.4 months of IM therapy duration and sustained UMRD duration prior to discontinuation, respectively relapsed at 53.2 months after IM discontinuation. Despite re-achieving MMR 1.4 later after IM restarting, the patient suddenly progressed to blast crisis at 6 months after restarting IM. Conclusions Our results showed that IM discontinuation can be applied with approximately 55% of probability of sustained MMR in the long term. Although sudden blast crisis occurring in responding patients with CML has already been reported in IM therapy, event of progression to BC in a clinical trial of IM discontinuation deserves to be followed-up with caution. Overall, both UMRD and IM duration on treatment were the most important predictors for successful IM-off. Disclosures Kim: Pfizer: Research Funding; Ilyang: Research Funding; Novartis: Research Funding; BMS: Research Funding.

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Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01562-z ◽

2021 ◽

Author(s):

E. Sala ◽

G. Carosi ◽

G. Del Sindaco ◽

R. Mungari ◽

A. Cremaschi ◽

...

Keyword(s):

Median Time ◽

Pituitary Surgery ◽

Somatostatin Analogues ◽

Exclusion Criterion ◽

Single Centre ◽

Disease Evolution ◽

Single Centre Experience ◽

Pituitary Irradiation

Abstract Purpose A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. Methods We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008–2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. Results In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24–84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3–12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66–150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. Conclusion A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

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Quantitative, Dynamic 18F-FDG PET/CT in Monitoring of Smoldering Myeloma: A Case Report

Diagnostics ◽

10.3390/diagnostics11040649 ◽

2021 ◽

Vol 11 (4) ◽

pp. 649

Author(s):

Christos Sachpekidis ◽

Matthias Türk ◽

Antonia Dimitrakopoulou-Strauss

Keyword(s):

Bone Marrow ◽

Plasma Cells ◽

Autologous Transplantation ◽

Standardized Uptake Value ◽

Focal Lesions ◽

Fdg Uptake ◽

Pet Ct ◽

18F Fdg ◽

Smoldering Myeloma

We report on a 52-year-old patient with an initial diagnosis of smoldering myeloma (SMM), who was monitored by means of dynamic and static positron emission tomography/computed tomography (PET/CT) with the radiotracer 1⁸F-fluorodeoxyglucose (18F-FDG). Baseline PET/CT revealed no pathological signs. Six months later, a transition to symptomatic, multiple myeloma (MM) was diagnosed. The transition was not accompanied by focal, hypermetabolic lesions on PET/CT. However, a diffusely increased 18F-FDG uptake in the bone marrow, accompanied by a marked increase of semi-quantitative (standardized uptake value, SUV) and quantitative, pharmacokinetic 18F-FDG parameters, was demonstrated. After successful treatment, including tandem autologous transplantation, the diffuse uptake in the bone marrow as well as the semi-quantitative and quantitative parameters showed a marked remission. This response was also confirmed by the clinical follow-up of the patient. These findings suggest that in MM a diffuse 18F-FDG uptake in the bone marrow may indeed reflect an actual bone marrow infiltration by plasma cells. Moreover, SUV values and kinetic parameters, not only from myeloma lesions but also from random bone marrow samples, may be used for MM monitoring. This could be particularly helpful in the follow-up of myeloma patients negative for 18F-FDG-avid focal lesions.

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Opiate dependence and pregnancy: 20-year follow-up study

Psychiatric Bulletin ◽

10.1192/pb.bp.106.011585 ◽

2007 ◽

Vol 31 (12) ◽

pp. 450-453 ◽

Cited By ~ 2

Author(s):

Marie Whitty ◽

John O'Connor

Keyword(s):

Psychosocial Functioning ◽

Substance Misuse ◽

Opiate Dependence ◽

Drug Misuse ◽

Clinical Implications ◽

Follow Up Study ◽

Treatment Centre ◽

Long Term Follow Up

AIMS AND METHODThis study examined the 20-year outcome of 55 women who were pregnant and using opiates in 1985 and were attending the Drug Treatment Centre and Advisory Board, Dublin. We established outcome across a number of variables, including mortality, psychiatric and physical morbidity, psychosocial functioning, ongoing drug misuse and outcome of offspring.RESULTSAt 20-year follow-up 29 women (53%) were deceased. HIV was the commonest cause of death, accounting for 17 deaths (59%). Those who were alive at follow-up displayed high rates of unemployment (84%), illicit substance misuse (74%) and most were dependent on state-subsidised accommodation (78%).CLINICAL IMPLICATIONSMortality was higher in our group compared with other long-term follow-up samples. These findings suggest that such participants and their offspring require intensive long-term support and treatment.

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Abstract TP127: Mortality and Recurrence in Atherosclerotic Ischemic Stroke: Long-term Follow-up

Stroke ◽

10.1161/str.48.suppl_1.tp127 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Miguel A Barboza ◽

Rodrigo Uribe ◽

Fabiola Serrano ◽

Luis C Becerra-Pedraza ◽

D. K Mantilla-Barbosa ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcome ◽

Median Time ◽

Smoking History ◽

Stroke Recurrence ◽

Active Smoking ◽

Long Term Outcome ◽

Long Term Follow Up

Background and purpose: Atherosclerotic ischemic stroke is the second most frequent etiology of stroke in the adult population. Functional outcome, mortality and recurrence of stroke rates on the long-term follow-up are poorly studied. This study investigates long-term outcome among patients with ischemic stroke secondary to atherosclerotic causality, and identifies the main factors associated with poor outcome, recurrence, and death. Methods: We analyzed data from our consecutive acute ischemic stroke database, over a period of 25 years (1990-2015). The endpoints were: bad outcome (Modified Rankin Score ≥3), recurrence and mortality at discharge, and final follow-up. Multivariate Cox and Kaplan-Meier analysis were used to estimate the probability of death and recurrence. Results: A total of 946 consecutive atherosclerotic stroke patients were included (571 [60.4%] males, median age 65 years [interquartile range 57-73 years] for the entire population); dyslipidemia (64.2%), hypertension (63.3%), diabetes (35.0%), and active smoking history (31.8%) were the most prevalent risk factors.After a median follow-up of 38 months (IQR 12-75 months), 59.3% patients had a bad outcome at discharge. A result of 26.1% had stroke recurrence (median time until recurrence: 9 months [IQR 12-84 months], with 12.9% cases presenting ≥2 recurrences), and 24.1% were dead (median time to death: 18.5 months [IQR 11-74 months]) at the final follow-up period. After multivariate adjustment, hypertension (HR 4.2, CI 95% 2.8-6.1; p<0.001) was the strongest predictor of recurrence. Additionally, diabetes (HR 2.6, CI 95% 2.0-3.5; p<0.001), bad functional outcome after recurrence (HR 2.3, CI 95% 1.9-2.9; p<0.001), age ≥65 years (HR 2.2, CI 95% 1.7-2.9; p<0.001), and active smoking (HR 1.8, CI 95% 1.3-2.3; p<0.001) were the strongest predictors of mortality. Conclusions: Atherosclerotic ischemic stroke has a high rate of recurrence, associated mainly with hypertension. Mortality is predicted by diabetes, bad functional outcome at recurrence, and older age.

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Positive outcome in a high-grade myxofibrosarcoma: a case report

Romanian Journal of Orthopaedic Surgery and Traumatology ◽

10.2478/rojost-2018-0007 ◽

2018 ◽

Vol 1 (1) ◽

pp. 27-30

Author(s):

Mihaela Olaru ◽

Cornelia Nitipir

Keyword(s):

Case Report ◽

Fibrous Histiocytoma ◽

Tumor Resection ◽

Pulmonary Nodules ◽

Positive Outcome ◽

Pet Ct ◽

Longus Muscle ◽

Long Term Follow Up

AbstractMyxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common sarcomas of the limb. It is usually treated multimodally. Most frequent sites of metastasis are the bone, lung and lymph nodes. The present paper is a case report of a 65-year-old male with myxofibrosarcoma of the fibularis longus muscle, for which he first underwent surgery - tumor resection with appropriate margins. The tumor was staged pT2b cN0 cM0. Postoperative PET-CT revealed metabolically inactive pulmonary nodules. Two months after surgery, he underwent adjuvant radiotherapy, a total dose of 60 Gy and 6 courses of chemotherapy (doxorubicin and ifosfamide). Pulmonary nodules have been stationary on all subsequent imagistic studies. He is free of recurrence on long-term follow-up.

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Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽

10.1182/blood-2019-129274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2352-2352

Author(s):

Tomas Jose Gonzalez-Lopez ◽

Fernando Fernandez-Fuertes ◽

Maria Cristina Pascual Izquierdo ◽

Isabel Caparros ◽

Silvia Bernat ◽

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Keyword(s):

Platelet Count ◽

Median Time ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Previous Treatment ◽

Complete Response ◽

Platelet Response ◽

Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

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