Uniform Approach Better Defines Natural History of Transient Myeloproliferative Disorder (TMD) in Down Syndrome (DS) Neonates: Outcomes from Children’ Oncology Group (COG) Study A2971.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 376-376
Author(s):  
Mukta Sharma ◽  
Todd A. Alonzo ◽  
April Sorrell ◽  
Robert B. Gerbing ◽  
Joanne M. Hilden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Natural History ◽  
Median Time ◽  
Hepatic Dysfunction ◽  
Risk Groups ◽  
Spontaneous Resolution ◽  
Life Threatening ◽  
History Of ◽  
Bone Marrow Blasts

Abstract TMD is solely found in DS infants in the first few months of life & is distinguished from congenital AML primarily by its spontaneous resolution. A2971, the largest study of TMD conducted to date, defines the natural history of this disorder by utilizing uniform observation & treatment guidelines. A total of 136 DS patients (pts) <90 days (d) of age were enrolled from 1999–2004 with median follow-up of 745d(0–2187). Pts were assigned to observation(n=110) or intervention(n=26) arms based upon clinical severity. Median age at diagnosis was 5d(0–58) with median hematologic values of WBC 32,800(4,800 – 259,100), hemoglobin 15(5–22.5), platelets 125K(10–958K), peripheral blasts 25%(0–92) & bone marrow blasts 15%(0–95). Hepatomegaly (HM) was seen in 59%, splenomegaly in 39%, & pleural or pericardial effusion in 10% & 19%. Pts required intervention due to hyperviscosity(11%), blast count >100,000/μl(25%), organomegaly(OM) with respiratory(resp) compromise(43%), CHF(11%), hydrops fetalis(21%), liver dysfunction(43%), renal dysfunction(14%), or DIC(25%). For pts who required intervention(n=29, 21%), 9 pts(31%) received leukopheresis/exchange transfusion (Leuk/Exch). 26(90%) pts received low-dose AraC (3.33 mg/kg/24 hrs continuous infusion on days 0–4) for OM, organ dysfunction causing resp compromise, or continued symptoms after Leuk/Exch. Among all pts, 3-year overall survival(OS) was 77 ± 8% & event-free survival(EFS) was 73 ± 9%. 28 deaths were noted (15 related, 12 unrelated to TMD or therapy, 1 unknown). Median time to TMD resolution (defined as resolution of peripheral/ bone marrow blasts, OM, effusions & organ dysfunction) was 46d(7–757). Peripheral blast resolution was attained in a median of 35d (2–147). To date, 16 pts (12%), including 4 treated with AraC, developed AML/MDS at a median time of 355d(118–888). We identified 3 distinct groups of TMD pts: low risk (without palpable HM or hepatic dysfunction, n=52, 38%), intermediate risk (HM with non-life threatening hepatic dysfunction, n=55, 40%), & high risk (WBC>100K or life threatening cardio-resp compromise due to TMD, n=29, 21%). The OS for low, intermediate & high risk groups was 92 ± 8%, 82 ± 11% & 49 ± 20% and EFS was 83 ± 11%, 64 ± 15% & 36 ± 19%, respectively(p<0.001 for low vs high & intermediate vs high risk groups for OS & EFS). WBC >100K (Hazards Ratio-HR 3.57, p=0.004) & presence of hepatomegaly (HR 3.6, p=0.009) were significant adverse risk factors for OS in univariate analyses. This study confirms that most TMD pts undergo spontaneous resolution of disease without intervention, further clarifies the natural history of TMD, & provides baseline comparisons for upcoming COG trials.

scholarly journals Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6752-6759 ◽  
Author(s):  
Alan S. Gamis ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Joanne M. Hilden ◽  
April D. Sorrell ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Natural History ◽  
Trisomy 21 ◽  
Myeloid Leukemia ◽  
Clinical Findings ◽  
Myeloproliferative Disorder ◽  
Spontaneous Resolution ◽  
Transient Myeloproliferative Disorder ◽  
Life Threatening ◽  
History Of

Abstract Transient myeloproliferative disorder (TMD), restricted to newborns with trisomy 21, is a megakaryocytic leukemia that although lethal in some is distinguished by its spontaneous resolution. Later development of acute myeloid leukemia (AML) occurs in some. Prospective enrollment (n = 135) elucidated the natural history in Down syndrome (DS) patients diagnosed with TMD via the use of uniform monitoring and intervention guidelines. Prevalent at diagnosis were leukocytosis, peripheral blast exceeding marrow blast percentage, and hepatomegaly. Among those with life-threatening symptoms, most (n = 29/38; 76%) received intervention therapy until symptoms abated and then were monitored similarly. Organomegaly with cardiopulmonary compromise most frequently led to intervention (43%). Death occurred in 21% but only 10% were attributable to TMD (intervention vs observation patients: 13/14 vs 1/15 because of TMD). Among those solely observed, peripheral blasts and all other TMD symptoms cleared at a median of 36 and 49 days from diagnosis, respectively. On the basis of the diagnostic clinical findings of hepatomegaly with or without life-threatening symptoms, 3 groups were identified with differing survival: low risk with neither finding (38%), intermediate risk with hepatomegaly alone (40%), and high risk with both (21%; overall survival: 92% ± 8%, 77% ± 12%, and 51% ± 19%, respectively; P ≤ .001). Among all, AML subsequently occurred in 16% at a median of 441 days (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov as NCT00003593.

Natural History of Paroxysmal Nocturnal Hemoglobinuria Clones In Patients Presenting as Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4428-4428
Author(s):  
Jeffrey J Pu ◽  
Galina Mukhina ◽  
Hao Wang ◽  
William Savage ◽  
Robert A Brodsky
Keyword(s):  
Bone Marrow ◽  
Natural History ◽  
Aplastic Anemia ◽  
Median Time ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Clone Size ◽  
Hematopoietic Stem ◽  
History Of ◽  
Pnh Clone ◽  
Ldh Value

Abstract Abstract 4428 Introduction: Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are closely related bone marrow failure disorders. Most AA results from an autoimmune attack directed against hematopoietic stem/progenitor cells. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a PIG-A mutation. The PIG-A gene mutation leads to glycosylphosphatidylinositol-anchor protein (GPI-AP) biosynthesis deficiency and subsequent hemolysis secondary to the absence of complement regulatory proteins (CD55 and CD59). Both PNH and AA can be cured by allogeneic bone marrow transplantation (alloBMT), but only a minority of patients is offered this approach due to the potential morbidity and mortality. AA can be treated with immunosuppressive therapy (IST) and PNH can be controlled by eculizumab. It has been estimated that more than 50% of AA patients harbor small, but expandable PNH populations at diagnosis. The natural history of PNH clones in AA patients following non-transplant therapy is not well studied. The purpose of this study is to determine the fate and clinical relevance of these PNH clones in patients with AA who did not receive an alloBMT. Patients and Method: Twenty-seven patients with AA and a detectable PNH clone were monitored for a median of 5.3 years (range,1.5 to 11.5 years). The PNH granulocyte clone sizes were measured using flow cytometry and analyzed via CellQuest software. PE-conjugated anti-CD15 and fluoresceinated aerolysin variant (FLAER) staining were used to define granulocytes and GPI-AP deficient cells respectively. Serum lactate dehydrogenase (LDH) value was used as a surrogate for monitoring hemolysis and 1.5× the upper limit of normal LDH value (330mg/dL) as a cut-off point to define clinically apparent hemolysis. A PNH size change <2.5% was considered as stable. Patients were treated with IST, HiCy, or both. Result: We found a linear relationship between PNH granulocyte clone size and LDH values (Pearson correlation coefficient=0.73; P<0.0001). A PNH clone size above 23% was the threshold to identify hemolysis as measured by LDH (ROC analysis with AUC=0.88). Higher LDH values over the period of follow-up were associated with larger PNH granulocyte clone size at diagnosis (P=0.03). Patients with small (≤15%) initial PNH granulocytes had lower LDH levels at 5 years after diagnosis (mean±SD: 236.9±109.9 vs 423.1±248.8; P=0.02), and were less likely to develop hemolysis (13.3% vs 55.6%, P=0.06) comparing to those with larger (>15%) initial PNH granulocytes. Of 9 patients who initially were treated with traditional IST (ATG, CsA, and prednisone), 7 did not respond to treatment and eventually received high-dose cyclophosphamide (HiCy) salvage therapy, 2 achieved a remission and did not require further treatment though one demonstrated PNH clone size expansion to 50% after 37 months. After HiCy salvage, all 7 patients became transfusion independent and 4 of them had no further PNH clone expansion. PNH clone expansion was observed in 7 of 9 patients at a median time of 3 (range: 2 to 87) months after treatment. Of 15 patients who received HiCy as initial therapy, 14 achieved remissions. Later expansion of PNH size was observed in 7 patients, of which 5 eventually required intermittent blood transfusion but only 1 developed symptomatic hemolysis necessitating eculizumab therapy. The median time to PNH granulocyte clone expansion after HiCy was 52 (range: 18 to 106) months. In 5 patients who received HiCy and then relapsed, their PNH clone size only increased (1±0.7)% in (71±31) months observation during post treatment remission; however, their PNH clone size increase accelerated to (38±14)% in (34±21) months after AA relapse (P=0.04). Two nSAA patients with an initial PNH clone size ≤15% spontaneously recovered hematopoiesis at 84 and 56 months respectively, neither had PNH clone size expansion. In this study, 25.9% patients kept a stable PNH size, 48.1% patients increased the size, and 26% patients decreased the size. The group with small initial PNH clone sizes (≤15%) was the most stable over time. Conclusion: The risk of developing clinically significant PNH over 10 years appears to be low in AA patients with PNH clones, especially for those with small initial PNH granulocyte clones (≤15%) and for those who maintain remission following therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The spontaneous resolution of a vortex vein varix: case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara L Weidmayer ◽  
Hakan Demirci
Keyword(s):  
Case Report ◽  
Natural History ◽  
Extended Period ◽  
Spontaneous Resolution ◽  
Case Presentation ◽  
Clinical Resolution ◽  
History Of ◽  
Vortex Vein ◽  
Insight Into

Abstract Background The natural course of a vortex vein varix, though not well understood, has been known to remain stable. However, here we report a novel case of a vortex vein varix that resolved after an extended period of monitoring. Case presentation An asymptomatic 96-year-old Caucasian man was found to have a vortex vein varix. At his previous examination 13 months prior, his fundus was normal. At 13 months of observation, his vortex vein varix become clinically undetectable. Further follow-up confirmed continued absence of the varix. Conclusion This case demonstrates the development then clinical resolution of a vortex vein varix with no clear identifiable factors for its evolution. This case is novel and offers new insight into the natural history of some vortex vein varices, implicating venous congestion as an instigator and venous collateralization as its alleviator, suggesting that vortex vein varices are likely more common than previously reported since some may be temporary and under-identified.

Real-World Experience with Type I Endoleaks after Endovascular Repair of the Thoracic Aorta

2010 ◽  
Vol 76 (6) ◽  
pp. 599-605 ◽  
Author(s):  
Joshua D. Adams ◽  
Margaret C. Tracci ◽  
Sahir Sabri ◽  
Kenneth J. Cherry ◽  
John F. Angle ◽  
...  
Keyword(s):  
Natural History ◽  
Thoracic Endovascular Aortic Repair ◽  
Spontaneous Resolution ◽  
Type I ◽  
Single Center ◽  
Type I Endoleak ◽  
History Of ◽  
Aortic Pathologies ◽  
Initial Results

Endoleaks are a frequent complication of thoracic endovascular aortic repair (TEVAR) and will likely increase in incidence with application of the technique to more complicated aortic anatomy and a wider range of thoracic aortic pathologies. Management generally consists of aggressive repair of Type I endoleaks; however, the natural history of Type I endoleaks after TEVAR remains largely unknown. The purpose of this study was to examine the incidence and characteristics of Type I endoleaks and to evaluate clinical outcomes of patients with Type I endoleaks after TEVAR. A single-center retrospective review was performed on all patients who underwent TEVAR over a 4-year period. Type I endoleaks were detected in 21 per cent (27 of 129) of patients on post-deployment aortography or CT angiography. During a mean follow-up of 750.63 ± 483 days, 59 per cent (16 of 27) closed spontaneously; 30 per cent (eight of 27) required secondary endovascular intervention; and 11 per cent (three of 27) have persisted with no increase in maximum aortic diameter. No patients have died or required open surgical conversion as a result of their Type I endoleak. Although accurate predictors of spontaneous resolution of Type I endoleaks have yet to be definitively characterized, our initial results suggest that it may be safe to observe small Type I endoleaks given that a large percentage resolve spontaneously and no endoleak-related deaths have occurred.

scholarly journals Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 296-304 ◽  
Author(s):  
DC Roy ◽  
R Tantravahi ◽  
C Murray ◽  
K Dear ◽  
B Gorgone ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Natural History ◽  
Marrow Transplantation ◽  
Cytogenetic Analysis ◽  
Common Finding ◽  
Mixed Chimerism ◽  
Allogeneic Bone ◽  
Donor Cells ◽  
History Of

Mixed hematopoietic chimerism (MC) is a common finding after allogeneic bone marrow transplantation (BMT), but the natural history of this phenomenon remains unclear. To understand the evolution and the implications of this finding, we performed a prospective analysis of the development of mixed chimerism in 43 patients with hematologic malignancies who received bone marrow (BM) from human leukocyte antigen (HLA)-identical sibling donors. T-cell depletion in vitro with anti-T12 (CD6) monoclonal antibody and rabbit complement was used as the only method of graft-versus-host disease (GVHD) prophylaxis. Overall, MC was identified in peripheral blood (PB) and BM in 22 of 43 (51%) patients evaluated. MC was found by restriction fragment length polymorphism (RFLP) analysis in 21 of 40 (53%) patients, by cytogenetic analysis in 6 of 29 (21%) patients, and by red blood cell phenotyping in 4 of 9 (44%) patients. RFLP studies were performed at 0.5, 1, 3, 6, 9, and 12 months post-BMT and then every 6 months, and showed a high probability of developing MC in the first 6 months after BMT followed by stabilization after 12 months. Cytogenetic analysis was less sensitive in detecting MC. Once MC was detected after BMT, the percentage of recipient cells increased very slowly over more than 3 years of follow- up, and no patient reverted to complete donor hematopoiesis (CDH). Thus, recipient and donor cells remained in a relative state of equilibrium for prolonged periods that seemed to favor recipient cells over donor cells. Patient's disease, remission status, or intensity of the transplant preparative regimen did not influence the subsequent development of mixed chimerism. Early immunologic reconstitution was the only factor that correlated with the subsequent chimeric status of the patients. The percentage and absolute number of T3 (CD3) and T4 (CD4) positive cells at day 14 after BMT were significantly higher in the patients who maintained CDH but NK cell reconstitution was similar in both groups, suggesting that early reconstitution with T cells may play a role in preventing recovery of recipient cells after BMT. GVHD was also associated with maintenance of CDH, but the probability of relapse, survival, and disease-free survival was identical in patients with MC and CDH.

scholarly journals Natural History of Thoraco-abdominal Aneurysm in High-Risk Patients

2010 ◽  
Vol 51 (3) ◽  
pp. 785
Author(s):  
P.A. Hansen ◽  
J.M.J. Richards ◽  
A.L. Tambyraja ◽  
L.R. Khan ◽  
R.T.A. Chalmers
Keyword(s):  
High Risk ◽  
Natural History ◽  
Abdominal Aneurysm ◽  
High Risk Patients ◽  
Risk Patients ◽  
History Of

Letter to the Editor

PEDIATRICS ◽  
1978 ◽  
Vol 61 (6) ◽  
pp. 940-940
Author(s):  
Peter Camfield ◽  
Carol Camfield
Keyword(s):  
High Risk ◽  
Natural History ◽  
Randomized Trial ◽  
Febrile Seizure ◽  
Febrile Seizures ◽  
Prospective Randomized Trial ◽  
Risk Of Recurrence ◽  
Letter To The Editor ◽  
History Of ◽  
Phenobarbital Administration

The riddle of febrile seizures is that despite their high risk of recurrence (35% to 50%), the natural history of the disorder is benign for the vast majority of children.1 If daily phenobarbital administration for several years is to be recommended after the first febrile seizure, it must be shown to be exceedingly effective and safe. The commendable study of Woff et al. is the second2 prospective randomized trial with concurrent controls of the efficacy of phenobarbital to prevent recurrent febrile seizures.

Spontaneous resolution of a Chiari malformation with syringomyelia

2021 ◽  
Vol 14 (6) ◽  
pp. e241789
Author(s):  
Hadleigh Cuthbert ◽  
Joshua Pepper ◽  
Rupert Price
Keyword(s):  
Natural History ◽  
Literature Review ◽  
Chiari Malformation ◽  
Surgical Intervention ◽  
Chiari I Malformation ◽  
Spontaneous Resolution ◽  
Conservative Approach ◽  
Resonance Imaging ◽  
History Of ◽  
Chiari I

The Chiari I malformation (CM-I) is characterised by overcrowding of the posterior fossa and descent of the cerebellar tonsils and is associated with syringomyelia. With the increasing availability of magnetic resonance imaging, CM-I is placing a growing burden on neurosurgical services. However, its natural history remains poorly understood, and the timing and nature of surgical intervention is controversial. We present a case of a significant, symptomatic CM-I with associated syrinx which underwent complete spontaneous resolution over a 4-year period. Spontaneous regression of Chiari malformation and syringomyelia is exceedingly rare; a literature review reveals 15 other cases and only one case which underwent complete resolution. The present case and literature review suggest a more benign natural history of CM-I and support a more conservative approach to its management. Further studies are required to determine whether any factors can predict resolution for certain patient cohorts.

Latex Hypersensitivity in Children: Clinical Presentation and Detection of Latex-Specific Immunoglobulin E

PEDIATRICS ◽  
1995 ◽  
Vol 95 (5) ◽  
pp. 693-699
Author(s):  
Pamela L. Kwittken ◽  
Sharon K. Sweinberg ◽  
Donald E. Campbell ◽  
Nicholas A. Pawlowski
Keyword(s):  
High Risk ◽  
Immunoglobulin E ◽  
High Risk Patient ◽  
Latex Allergy ◽  
Patient Profile ◽  
Specific Immunoglobulin E ◽  
Specific Immunoglobulin ◽  
Life Threatening ◽  
History Of

Objective. To better understand the clinical characteristics, diagnosis, and possible prevention of immediate hypersensitivity reactions to latex in a hospitalized, pediatric patient population. Methods. We performed a retrospective case analysis of the first 35 patients with latex allergy evaluated by our service over a 2-year period at our institution. Characteristics of patients and clinical reactions were analyzed and the presence of latex-specific immunoglobulin E was assessed using in vitro methods. In a limited group of Objective. To better understand the clinical premedication with steroids and antihistamines was evaluated for the prevention of latex allergic reactions. Results. The majority of our patients had life-threatening reactions. In previous reports, most pediatric patients underwent reactions in the perioperative period and belonged to two well-recognized "high-risk" patient groups (spina bifida and genitourinary malformations). In our series, 21 patients (60%) had reactions outside of the operating room setting, and 14 patients (40%) had primary diagnoses outside of the previously recognized "high-risk" groups. Many patients had a history of multiple surgical procedures, and a history of a surgical procedure in the first year of life was very common. A pre-existing clinical history of latex allergy was present in only 18 of the 35 patients, and a severe or life-threatening allergic reaction was the presenting feature of latex allergy in 11 of the 35 patients. Using in vitro assays, we were able to detect latex-specific immunoglobulin E in the sera of all but two of our patients. Latex gloves and latex-containing intravenous sets were common triggers for reactions. When exposure to latex occurs systemically, as through an intravenous line, premedication with steroids and antihistamines may fail to protect against anaphylaxis. Conclusions. Our experience indicates that the incidence of latex hypersensitivity in children is increasing, that the circumstances (patient profile, hospital location, route of exposure) in which life-threatening reactions may occur are more broad than previously reported, and that a better understanding of both environmental sources of latex antigens and host responses to latex exposure are needed for improved prevention of serious reactions.

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