Clonality in Granulocytes Detected by an Improved HUMARA Assay: A Good Prognostic Marker in Bone Marrow Failure Patients Exhibiting Chromosomal Abnormalities of Indefinite Significance.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3702-3702
Author(s):  
Ken Ishiyama ◽  
Chiharu Sugimori ◽  
Hirohito Yamazaki ◽  
Akiyoshi Takami ◽  
Shinji Nakao
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Failure ◽  
Bone Marrow Examination ◽  
Refractory Anemia ◽  
Clonal Population ◽  
Dividing Cells ◽  
Humara Assay

Abstract Some patients with aplastic anemia (AA) and approximately 40% of patients with refractory anemia (RA) of myelodysplastic syndrome exhibit karyotypic abnormalities in bone marrow dividing cells. Although some of the patients undergo evolution to acute myeloid leukemia (AML), others follow a clinical course similar to AA patients without chromosomal abnormalities. Except for several abnormalities such as −7 and 5q-, the clinical significance of such chromosomal abnormalities in bone marrow failure patients remains unclear. We recently developed a reliable HUMARA assay capable of detecting a clonal population in granulocytes which constitutes 30% or more of total granulocytes (Blood. 2003;102:1211–1216). Studying correlation between chromosomal abnormalities and the presence of clonality may help in understanding the pathogenetic role of chromosomal abnormalities in AA and RA. We thus analyzed 50 acquired AA and 28 RA female patients who were heterozygous for the HUMARA gene. Chromosomal abnormalities such as add(5)(q13), 9q–9q+ and del(7)(q14q22) were found in 8% of AA and 21% of RA patients. Clonality was detected in 38% of AA patients and 39% of RA patients. Incidence of chromosomal abnormalities in patients with clonality (27%) was higher than that in patients without clonality (4%, p<0.01). In two AA patients who respectively exhibited add(5)(q13) in 10% and +8 in 38% dividing cells, clonality was not detected and these abnormal clones became undetectable at the time of subsequent bone marrow examination. Clonality was detected in the other 2 AA patients respectively exhibiting 9q–9q+ in 40% and del(7)(q14q22) in 25% dividing cells, and in all 5 RA patients respectively exhibiting +8 in 10%, del(5)(q13q31), dup(1)(q32q12) in 90%, del(5)(q13), add(11)(q23), inv(9) in 65% and X,-X in 100% of dividing cells. None of the 50 AA patients including 2 patients with clonality and chromosomal abnormalities underwent evolution to AML during 2-year follow up while one of 28 RA patients who exhibited del(5)(q13q31) progressed to AML. The proportion of clonal granulocytes in total granulocytes estimated by the HUMARA assay remained unchanged in most patients with clonality except for the transformed one. These data indicate that the chromosomal abnormality in bone marrow dividing cells is not necessarily associated with presence of clonal granulocyte population in peripheral blood and that detection of clonality in granulcytes in bone marrow failure patients with chromosomal abnormalities of indefinite significance is useful in predicting prognosis of these patients.

Intravenous Immunoglobulin Is an Effective Treatment for LGL-Mediated Immune Cytopenias in Myelodysplastic Syndromes and Other Bone Marrow Failure Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1704-1704
Author(s):  
Francesca Schieppati ◽  
Erin P. Demakos ◽  
Odchimar Rosalie-Reissig ◽  
Shyamala C. Navada ◽  
Lewis R. Silverman
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Intravenous Immunoglobulin ◽  
Hemolytic Anemia ◽  
Bone Marrow Failure ◽  
Myeloproliferative Neoplasm ◽  
Recurrent Fever

Abstract Background: Myelodysplastic Syndrome (MDS) and Aplastic Anemia (AA) are often associated with clinical immune manifestations. An abnormal profile of the T-cell repertoire can be detected in these patients (pts) and is thought to play a role in bone marrow (BM) insufficiency. The presence of a co-existent large granular lymphocytic (LGL) clone may exacerbate cytopenias independent of the primary disease mechanism and offers another target for therapeutic intervention. Treatment for LGL proliferation is usually immunosuppressive therapy but there is no accepted standard of care. Methods: We explored the role of intravenous immunoglobulin (IVIG) as a treatment for immune-related cytopenias, i.e. Coombs negative (C-) hemolytic anemia, in a series of 12 consecutive pts with an LGL clonal proliferation documented by flow cytometry and TCR clonal rearrangements. Of the 12 cases, 9 had MDS (7 lower-risk), 1 AA with LGL liver involvement, and 1 primary myelofibrosis. One patient (pt) had suspected MDS. Overall response was assessed by MDS IWG criteria 2006. We defined a hemolysis response (HLR) as complete normalization (CR) or, a greater than 50% improvement (PR) in deviation from normal values of LDH, reticulocytes, indirect bilirubin and haptoglobin. Duration of HLR was defined as the time from onset of HLR to the time of resumption of hemolysis and loss of effect of IVIG. Results: All pts were treated with IVIG administered at a dose of 500mg/kg of IVIG once per week, in repeated cycles, with a duration ranging from 1-4 week(s) per cycle. Clinical characteristics (Table 1): M/F ratio 10/2; median age 69. Ten pts had a CD3+ T-LGL and 2 had a CD3-/CD16+/CD56+ NK-LGL circulating clone. Karyotype abnormalities were non-specific; 8 pts had 1-3+ reticulin BM fibrosis; 4 had mutations in RNA-splicing genes: SF3B1 (2); SETBP1 (1); SRSF2 (1). Ten pts were evaluable for response: 8 pts responded (ORR 80%): Hematological improvement (HI-erythroid) 8/8 (100%); a hemolysis CR (HLR-CR) occurred in 7 (87.5%) and hemolysis PR (HLR-PR) in 1 pt (12.5%). Median number of cycles, follow up, and duration of treatment were 16, 21.5 and 9.5 months (mo), respectively. The HLR-CR was durable and prolonged in 3/8 (38%) pts; 2 of these 3 pts (67%) did not require maintenance IVIG. Relapse from HLR occurred in 4, during infection or chemotherapy, but the response returned to the original level by shortening the intervals between administration of IVIG. One pt had relapsed after an initial response and then became refractory to IVIG. In follow up at month 38, 75% of pts were still responding to treatment, and 1 pt was still in remission after 46 mo. In 4 of 6 pts, corticosteroid treatment was discontinued and no longer required for chronic hemolysis, with general improvement of steroid related symptoms. Some patients had been on steroids maintenance for periods ranging from months to years. Response was more durable with continuous rather than sporadic dosing. Adverse events were not specific: 1 pt with self-limited isolated palpitations; 1 pt with hypertension not requiring intervention. Conclusions: Treatment with IVIG of immune cytopenias associated with LGL clones and BMF yields durable responses in 80% of pts. IVIG, especially at high concentrations, may enhance apoptosis, suppress proliferation of T-cells and induce immune-regulation. Given the relative rarity of LGL clones in MDS, further investigational studies will help define the role of IVIG and clarify the mechanism of action in this group of pts with MDS and BMF associated with LGL clones. Table 1. Variable Observed % Symptomatic anemia (fatigue, SOB) 9/12 75 B symptoms (recurrent fever) 2/12 16.6 Infections (bacteremia Campylobacter with migratory arthritis and dermatitis; cellulitis bacteremia S. epidermidis and osteomyelitis) 2/12 16.6 Skin lesions (leg focal ulceration and dermal fibrosis) 1/12 8.3 Splenomegaly 7/12 58.3 Hepatomegaly 2/12 16.6 Adenopathy (mediastinal) 1/12 8.3 Neuropathy 2/12 16.6 Hematologic disorders 11/12 91.6 Myelodysplastic syndrome 9/12 75 Severe aplastic anemia 1/12 8.3 Myeloproliferative neoplasm (PMF) 1/12 8.3 Lymphoproliferative neoplasm (FL+MDS) 1/12 8.3 Hemolytic anemia 11/12 91.6 Solid tumors (anal, squamous cell; breast ca) 2/12 16.6 Autoimmune disorders 7/12 58.3 ITP 3/7 42.8 Ulcerative colitis 1/7 14.3 Pernicious anemia 1/7 14.3 Systemic lupus erythematosus 1/7 14.3 Immune pancreatitis 1/7 14.3 MGUS 4/12 33.3 Disclosures Off Label Use: IVIG.

scholarly journals Polyclonal hematopoiesis maintained in patients with bone marrow failure harboring a minor population of paroxysmal nocturnal hemoglobinuria–type cells

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1211-1216 ◽  
Author(s):  
Ken Ishiyama ◽  
Tatsuya Chuhjo ◽  
Hongbo Wang ◽  
Akihiro Yachie ◽  
Mitsuhiro Omine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Positive Response ◽  
Bone Marrow Failure ◽  
Refractory Anemia ◽  
Clonal Population ◽  
Inactivation Pattern ◽  
Minor Population ◽  
A Minor

Abstract Although a minor population of paroxysmal nocturnal hemoglobinuria (PNH)–type blood cells is often detected in patients with aplastic anemia (AA) and refractory anemia (RA), the significance of such cells in the pathophysiology of bone marrow (BM) failure remains obscure. We therefore examined clonality in peripheral blood granulocytes from 118 female patients with AA or myelodysplastic syndrome using the X chromosome inactivation pattern. Clonality, defined as a clonal population accounting for 35% or more of total granulocytes, was confirmed in 22 of 68 (32.4%) AA patients, in 13 of 44 (29.5%) RA patients, in all 4 RA with excess blasts (RAEB) patients, and in 4 patients with PNH. When the frequency of patients with granulocyte clonality was compared with respect to the presence of increased PNH-type cells, the frequency was significantly lower in AA patients with (PNH+; 21.2%) than without (PNH–; 42.9%) increased numbers of PNH-type cells (P = .049). Clonality was absent in granulocytes from the 15 PNH+ RA patients but present in 13 of 29 (44.8%) PNH– RA patients (P = .0013). The absence of clonality in AA and RA patients before treatment was strongly associated with positive response to immunosuppressive therapy (without clonality, 74.4%; with clonality, 33.3%; P = .0031) in all patients as well as in PNH+ patients (without clonality, 96.2%; with clonality, 66.6%, P = .026). These results suggest that AA and RA with a minor population of PNH-type cells are benign types of BM failure with immune pathophysiology that have little relationship to clonal disorders such as RAEB or acute myeloid leukemia.

Central Morphology Review of Childhood Bone Marrow Failure in Japan

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1604-1604 ◽  
Author(s):  
Asahito Hama ◽  
Manabe Atsushi ◽  
Daisuke Hasegawa ◽  
Kazue Nozawa ◽  
Yusuke Okuno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Who Classification ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Failure ◽  
Severe Disease ◽  
Refractory Anemia ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Female Ratio ◽  
Cell Lineages

Abstract In the diagnosis of childhood bone marrow failure (BMF), differentiating aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (MDS) is challenging. In addition, inherited BMF (IBMF) should be excluded from acquired BMF. The 2008 WHO classification has proposed a provisional entitiy, “refractory cytopenia of childhood (RCC)”. The spectrum of patients with RCC is wide, ranging from patients with severe hypocellular bone marrow (BM) and mild dysplasia to those with normocellular BM and distinct dysplasia meeting the criteria for refractory cytopenia with multilineage dysplasia (RCMD) in adults. Currently, it is recommended that children who meet the criteria for RCMD should be considered as RCC in the WHO classification until the number of lineages involved have been fully evaluated with regard to their relative importance as prognostic factors in childhood MDS. To enable diagnosis based on the WHO classification, the Japanese Society of Pediatric Hematology and Oncology in February 2009 established a central review system of BM morphology, including peripheral blood (PB) and BM smears and specimens from trephine biopsies in childhood BMF. PB and BM smears were reviewed by two pediatric hematologists, and the specimens from BM trephine biopsies were reviewed by a pathologist. In addition, the telomere length of lymphocytes and paroxysmal nocturnal hemoglobinuria (PNH) clones in PB were measured by flowcytometry for patients with BMF. RCC is defined as persistent cytopenia with <2% and <5% blasts in PB and BM, respectively. BM aspirate smears show dysplastic changes in >2 cell lineages or >10% within one cell lineage. On the other hand, the criteria of RCMD in adult MDS is defined as persistent cytopenia with <1% and <5% blasts in PB and BM, respectively. BM smears show >10% dysplastic changes in >2 cell lineages. We introduced the RCMD criteria in this central review. From February 2009 to October 2013, 1,000 cases including 536 males and 464 females were prospectively reviewed. The median age was six years (range, 0–39 years). Of the 1,000 cases, 575 were classified as BMF, and of them, 137 were classified as AA, 236 as RCC, 103 as RCMD, 38 as hepatitis-related BMF, 3 as PNH and 58 as IBMF. Of the 58 cases with IBMF, 21 were diagnosed as Fanconi anemia, 12 as Shwachman–Diamond syndrome, and 8 as dyskeratosis congenita. Seventeen patients suspected of IBMF were undiagnosed. In 97 advanced cases of MDS, 24 were classified as refractory anemia with excess blasts (RAEB), 6 as secondary MDS, and 21 as therapy-related MDS. To determine the clinical differences among AA, RCC, and RCMD, we compared laboratory and clinical data for 476 patients classified as AA, RCC, and RCMD. Median ages in the AA, RCC, and RCMD groups were 9, 8, and 7 years, respectively (p = 0.007). The male/female ratio in AA, RCC, and RCMD groups was 1.1, 1.2, and 3.6, respectively (p = 0.034). When patients were classified according to the disease severity criteria for AA, 78% of the patients with AA had very severe or severe disease, whereas only 38% of the patients with RCC and 28% of the patients with RCMD had very severe or severe disease (p < 0.001). Chromosomal abnormalities were detected in two patients (1%) with AA (trisomy 8), 10 patients (4%) with RCC (monosomy 7, n = 2; trisomy 8, n = 6; other, n = 2), and 12 patients (12%) with RCMD (monosomy 7, n = 5; trisomy 8, n = 2; other, n = 5) (p = 0.001). Out of the 476 patients, 67 (AA, n = 32; RCC, n = 32; RCMD, n = 3) were administered IST with rabbit antithymocyte globulin (ATG) and cyclosporine. After 6 months, the response rate to IST was not significantly different among the three groups; AA, 41%; RCC, 47%; RCMD, 100% (p = 0.142). In conclusion, the entity of RCMD should be applied to childhood MDS because patients with RCMD exhibited a significantly high frequency of chromosomal abnormalities at the time of diagnosis. To definitively determine whether these three diseases are different entities, it would be necessary to prospectively compare the clinical outcomes and biological findings in a larger number of patients with AA, RCC, and RCMD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hevylite and Freelite Tests in Newly Diagnosed Multiple Myeloma: Clinical Utility and Correlations with Clinical Features

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5625-5625
Author(s):  
Paola Omedé ◽  
Valter Redoglia ◽  
Monica Astolfi ◽  
Alessandra Larocca ◽  
Stefano Spada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Research Funding ◽  
Chromosomal Abnormalities ◽  
Advisory Board ◽  
Bone Marrow Infiltration ◽  
Newly Diagnosed

Abstract Introduction Heavy light chain (HLC) assay is a recently developed method that separately quantifies the k and L-bounded amounts of a given intact immunoglobulin (Ig). It allows an accurate quantification of both the involved/uninvolved Ig and permits to quantify even small monoclonal protein. Free light chain (FLC) and HLC can provide prognostic information for multiple myeloma patients. We evaluated the role of HLC and FLC tests in the assessment and evolution of the disease in newly diagnosed multiple myeloma (MM) patients. Methods From February 2011 to April 2014, 1510 patients aged ≤65 years with symptomatic newly diagnosed MM were enrolled in the EMN02/HO95 study. Details about treatments and preliminary results of the main study were previously reported (Cavo M et al, abs8000, J Clin Oncol 34, 2016). In this analysis, we focused on patients enrolled in Italy (N=718). Serum samples from each enrolled patient were collected at diagnosis, before starting maintenance, and thereafter every 6 months. Samples from 665 patients at diagnosis and 156 at pre-maintenance were analyzed. Involved HLC ratio (iHLCR) was calculated with the involved Ig (either G or A) as numerator. Involved FLC ratio (iFLCR) was calculated as K/L or L/K with the monoclonal chain as numerator. FLC ratio (FLCR) and HLC ratio (HLCR) were calculated as K/L. The analyses were performed using Spearman correlation. Results Median follow-up was 32 months. At baseline the type of paraprotein was IgG in 428 (298 IgG-k, 130 IgG-L), IgΑ in 123 (77 IgΑ-k, 46 IgΑ-L) or light chain in 104 patients (k 73, L 31); 10 patients were IgD or IgM. International Staging System (ISS) stages were well distributed in all the isotypes. The median involved HLC values were IgG-K 28.97, IgG-L 30.6, IgA-K 41.7, IgA-L 35.7 g/L, light chain K 2719.58 mg/L, and light chain L 3369.75 mg/L. HLC IgG was significantly correlated with B2-microglobulin (r=0.31), extensive bone marrow infiltration >60% (r=0.31) and hemoglobin (r=-0.39). HLC IgA was not correlated with any disease parameter. In light chain MM, iFLC was correlated to B2-microglobulin (r=0.41), creatinine (r=0.39), extensive bone marrow infiltration >60% (r=0.39) and hemoglobin (r=-0.36). The increase of iFLCR (≥ median value) was significantly associated with IgG, ISS III, anemia, extensive bone marrow infiltration and higher creatinine (p<0.001), but not with the presence of high risk chromosomal abnormalities. High iFLCR (> third quartile) was significantly associated with inferior TTP (median 43.4 versus NR, HR 1.75 95% CI 1.22-2.53, p 0.003). The increase of iHLCR (≥ median value) was significantly associated with ISS III, anemia, and extensive bone marrow infiltration (p<0.001), whereas the presence of high risk chromosomal abnormalities was not. At pre-maintenance, 17% of patients had an abnormal HLCR, whereas 82% had a normalization of HLCR. The normalization of HLCR before starting maintenance was significantly related with the achievement of complete response (CR) (p=0.02) and a trend towards a longer 3-years TTP was observed (83% versus 74%, Log-rank test 0.05). Before start of maintenance, 27% of patients had a normalization of FLCR. No significant correlation with response or outcome was observed for patients who had a normalization of FLCR. At pre-maintenance, 67% IgG or IgA MM patients were immunofixation (IFX) negative. Among them, 8% had still an abnormal HLCR compared to IFX positive patients (8% versus 36%, p<0.001). Conclusions This preliminary analysis confirms the prognostic role of high iFLCR and iHLCR in newly diagnosed MM patients. HLCR normalization may be a valuable parameter to better define CR and predict outcome. HLC can quantify even small monoclonal protein when immunofixation is negative. Further follow-up is needed to assess the prognostic impact of HLC and FLC on survival outcome. Updated results will be presented at the meeting. Disclosures Larocca: Janssen-Cilag: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Cavo:Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria. Petrucci:Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria. Patriarca:Bristol-Myers Squibb: Other: Advisory board; Mundipharma: Other: Advisory board; MSD: Consultancy; Janssen-Cilag: Other: Advisory board; Celgene: Consultancy. Corradini:Takeda: Consultancy, Speakers Bureau; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Servier: Honoraria; Gilead: Honoraria, Speakers Bureau; Gentium: Honoraria, Speakers Bureau. Sonneveld:Celgene: Other: Advisory board, Research Funding; Onyx: Other: Advisory board, Research Funding; Millennium: Other: Advisory board, Research Funding; Janssen-Cilag: Other: Advisory board, Research Funding. Boccadoro:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; SANOFI: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Abbivie: Honoraria; Mundipharma: Research Funding. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria.

Clinical Significance of Chromosomal Abnormalities in Patients with Aplastic Anemia and Refractory Anemia Deduced From the Prevalence of PNH-Type Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1085-1085
Author(s):  
Naomi Sugimori ◽  
Hirohito Yamazaki ◽  
Chiharu Sugimori ◽  
Ken Ishiyama ◽  
Takamasa Katagiri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Significance ◽  
Chromosomal Abnormality ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Failure ◽  
Normal Karyotype ◽  
Refractory Anemia ◽  
Fish Analysis ◽  
Immune Mediated ◽  
High Prevalence

Abstract Abstract 1085 Poster Board I-107 Background Benign types of bone marrow failure such as aplastic anemia (AA) and refractory anemia (RA) of MDS defined by the FAB classification occasionally present various chromosomal abnormalities, although the clinical significance of each abnormality is unclear. Small populations of CD55-CD59- granulocytes and erythrocytes are detected in approximately 50% of patients with AA and 15% of patients with RA (Br J Haematol 2009). Analyzing the relationship between the presence of a certain chromosomal abnormality and PNH-type cells may be useful in deducing the clinical significance of the karyotype abnormalities because such PNH-type cells represent a good marker for the benign bone marrow failure with immune pathophysiology. Patients and Methods From 1995 through 2009, peripheral blood from 2487 patients with AA or RA was examined for the presence of PNH-type cells using high sensitivity flow cytometry. Chromosome data on bone marrow cells were available in 1513 patients. The proportion of patients possessing PNH-type cells was determined in a subset of AA or RA defined by various chromosomal abnormalities. The sorted PNH-type granulocytes from some patients with chromosomal abnormalities were subjected to FISH analysis to determine the origin of the cells. Results Chromosomal abnormalities were detected in 16% of the patient population, 11% (59/546) in patients possessing PNH-type cells (PNH+ patients) and 19% (186/967) in patients without increased PNH-type cells (PNH- patients). The most frequent chromosomal abnormalities were trisomy 8 (+8) (3.6%), deletion of 20q (del(20q)) (2.4%), deletion of 13q (del(13q)) (1.0%), monosomy 7 (-7) (0.5%), deletion of 5q (del(5q)) (0.3%) in order of descending prevalence. The proportion of PNH+ patients in each patient group defined by chromosomal abnormality was 24%, 14%, 73%, 0% and 0% respectively. The proportion of PNH+ patients in patients with normal karyotype was 35%. Notably, patients with del(13q) showed a remarkably high prevalence of PNH-type cells (73%), even significantly higher than the prevalence of the patients without chromosomal abnormalities (P<0.01). The high prevalence of PNH-type cells was compatible with the previous finding that patients with del(13q) were likely to respond to immunosuppressive therapy (Br J Haematol, 2002). On the other hand, the proportion of PNH+ in patients with +8 and del(20q) or -7 was significantly lower than that of patients without chromosomal abnormalities (P<0.05, P<0.01 and P<0.05). In particular, none of the patients with -7 and del(5q) showed PNH-type cells, indicating the pathophysiology of the bone marrow failure with these chromosomal abnormalities to be non-immune mediated. FISH analysis of sorted PNH-type granulocytes showed the normal karyotype, indicating the PNH-type cells were derived from normal karyotype cells. Conclusions The presence of del(13q) in AA or RA represents benign bone marrow failure associated with a good response to immunosuppressive therapy, while the presence of -7 and del(5q) is thus considered to be related to a non-immune pathophysiology. AA and RA with +8 or del(20q) comprise a small subset of immune-mediated bone marrow failure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nontransplant therapy for bone marrow failure

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Danielle M. Townsley ◽  
Thomas Winkler
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Single Agent ◽  
Telomere Attrition ◽  
Long Term Follow Up ◽  
Treatment Naïve

Abstract Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease. Danazol, which is traditionally less preferred for treating cytopenias, is capable of preventing telomere attrition associated with hematologic responses in constitutional bone marrow failure resulting from telomere disease.

scholarly journals Chromosome 10 Abnormality Predicts Prognosis of Neuroblastoma Patients With Bone Marrow Metastasischromosome 10 Abnormality Predicts Prognosis of Neuroblastoma Patients With Bone Marrow Metastasis

2021 ◽  
Author(s):  
Chiyi Jiang ◽  
Xiao Xu ◽  
Binglin Jian ◽  
Xue Zhang ◽  
Zhixia Yue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Characteristics ◽  
Chromosomal Abnormalities ◽  
Abnormal Chromosome ◽  
Mycn Amplification ◽  
Chromosome 10 ◽  
Orbital Metastases ◽  
One Year ◽  
The Relationship

Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor in children with high heterogeneity and concealed onset. The mechanism for its occurrence and development has not been revealed. The purpose of this study was to summarize the clinical characteristics of children with NB and abnormal chromosome 10. To investigate the relationship between the number and structure of chromosome 10 abnormality and NB prognosis.MethodsWe used chromosome G-banding in the first diagnosis to evaluate the genetics of chromosomes in patients with NB, and follow up their clinical characteristics and prognosis. All participants were diagnosed with NB in Hematology Oncology Center, Beijing Children’s Hospital from May 2015 to December 2018, and were followed up for at least one year. ResultsOf all 150 patients with bone marrow metastases, 42 were clearly diagnosed with chromosomal abnormalities. There were 13 patients with chromosome 10 abnormalities definitely, and the loss of chromosome 10 was the most common decrease in the number of chromosomes. These 13 patient had higher LDH, lower OS and EFS than that of children in abnormal group without chromosome 10 abnormality. Eight patients both had MYCN amplification and 1p36 deletion. Two of them had optic nerve damage and no vision, and 1 had left supraorbital metastases five months after treatment. Among the 16 children with suspected chromosome 10 abnormalities, 3 also had orbital metastases. ConclusionsThe above results showed that chromosome 10 might be a new prognostic marker. MYCN amplification and 1p36 deletion may be related with chromosome 10 abnormalities in NB. And NB patients with abnormal chromosome 10 were prone to have orbital metastases.

scholarly journals The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Yong Tang ◽  
Marie J. Desierto ◽  
Jichun Chen ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transcription Factor ◽  
Transforming Growth Factor ◽  
Bone Marrow Failure ◽  
Critical Role ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Immune Mediated

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

scholarly journals Revesz syndrome revisited

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Michael Karremann ◽  
Eva Neumaier-Probst ◽  
Frank Schlichtenbrede ◽  
Fabian Beier ◽  
Tim H. Brümmendorf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
English Literature ◽  
Bone Marrow Failure ◽  
Dyskeratosis Congenita ◽  
Kaplan Meier ◽  
Low Prevalence

Abstract Background Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature. Methods To further characterize the typical features and natural course of the disease, we screened the English literature and summarized the clinical and epidemiological features of previously published RS cases. In addition, we herein describe the first recorded patient in central Europe. Results The literature review included 18 children. Clinical features are summarized, indicating a low prevalence of the classical DKC triad. All patients experienced early bone marrow failure, in most cases within the second year of life (median age 1.5 years; 95% CI 1.4–1.6). Retinopathy occurred typically between 6 and 18 months of age (median age 1.1 years; 95% CI 0.7–1.5). The incidence of seizures was low and was present in an estimated 20% of patients. The onset of seizures was exclusively during early childhood. The Kaplan–Meier estimate of survival was dismal (median survival 6.5 years; 95% CI 3.6–9.4), and none of the patients survived beyond the age of 12 years. Stem cell transplantation (SCT) was performed in eight children, and after a median of 22 months from SCT four of these patients were alive at the last follow up visit. Conclusion RS is a severe variant of DKC with early bone marrow failure and retinopathy in all patients. Survival is dismal, but stem cell transplantation may be performed successfully and might improve prognosis in the future.

Sign in / Sign up

Export Citation Format

Share Document