scholarly journals Prolonged Pyrexia due to Hemophaghocytic Lymphohistiocytosis

2015 ◽  
Vol 3 (2) ◽  
pp. 77-78
Author(s):  
Farzana Shumy ◽  
Tanvir Ahmed ◽  
Ahmad Mursel Anam ◽  
Abed Hussain Khan ◽  
Mohammad Ferdous Ur Rahaman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Clinical Features ◽  
Serum Ferritin ◽  
Elevated Serum ◽  
Initial Presentation ◽  
Diagnostic Challenge ◽  
Diagnostic Difficulties ◽  
Clinical Illness

Haemophaghocytic lymphohistiocytosis (HLH) is an uncommon illness in adults. It is rare but common clinical features like lymphadenopathy, hepatosplenomegaly, fever are presentation of many different familiar clinical illness, make it a diagnostic challenge. Here, we present a case of a previously healthy young boy presented with fever and other features like hepatosplenomegaly, pancytopenia, markedly elevated serum ferritin, Lactate dehydrogenase, triglyceride, low fibrinogen, persistent hyponatremia and finally detectable Haemophagocytosis in his bone marrow. Unfortunately, diagnosis was delayed around 4 month after his initial presentation and he succumbed to his disease. This case highlights common clinical features and diagnostic difficulties have to face in making confirmed diagnosis of HLH.Bangladesh Crit Care J September 2015; 3 (2): 77-78

Significant Suppression of the Colony Forming Capacity of Erythroid Progenitors by Iron Overload in Patients with MDS and Sequential Anlyses of BFU-E Under Chelation Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3826-3826
Author(s):  
Julia Hartmann ◽  
Ursula Sinzig ◽  
Gerald Wulf ◽  
Lorenz Trümper ◽  
Frank Konietschke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Peripheral Blood ◽  
Chelation Therapy ◽  
Elevated Serum ◽  
Prognostic Impact ◽  
Erythroid Progenitors ◽  
Colony Assays ◽  
Colony Forming Capacity

Abstract Abstract 3826 Poster Board III-762 Introduction The majority of patients with MDS depend on regular blood cell (RBC) transfusions during the course of their disease. Patients with lower-risk MDS are at particularly high risk of developing iron overload because of their longer median survival. Transfusional iron overload is known to be associated with increased morbidity mainly due to cardiac and/or hepatic damage. As a result an excess mortality rate in polytransfused pts. has been demonstrated. A negative prognostic impact of transfusion need is a proven independent marker for a bad prognosis. Jensen et al. (1996) demonstrated that an adequate chelation therapy could improve the transfusion need of pts. with MDS significantly (Br J Haematol 1996, 94, 288-299). This observation was supported by recent findings of another group (Messa, Acta Haematol, 2008, 120, 70-4) with improvement of transfusion need under adequate chelation therapy. Thus iron overload might not only be harmful to hepatocytes and cardiomyocytes but also to bone marrow progenitor cells. Their function is intrinsically impaired by MDS itself and might be further affected by a “second hit” in the form of toxic iron overload which might additionally impair their colony forming capacity. Patients and methods We performed colony assays from the peripheral blood from 52 pts. with MDS (RA/RARS: n=18, RCMD/RS: 12, RAEB-I/II: 13, 5q-syndrome: 3, MDS-U: 2, CMML: 1, and others: 2; age: 39 – 86 yrs. (median: 68 yrs.); cytogenetics: normal: 26, 5q-: 6, -7/7q-: 2, complex: 4, others: 4) with (serum ferritin ≥250 μg/L, range: 273 – 6267 μg/L, median: 664 μg/L) and without iron overload (range: 11 – 213 μg/L). Only pts. without hepatic and/or active infectious diseases, without chemotherapy/epigenetic therapy during the last 6 months and without cytokine and/or corticoid therapy during the last 3 months before performance of colony assays were considered. BFU-E and CFU-GM were analysed by the same person (U.S.) after 12 – 16 days in cultures from peripheral blood, performed as described (Leuk Res, 2001; 25(11):955-9) in 14 (BFU-E)/ 12 (CFU-GM) pts. with normal ferritin-values (normal range: 20-250 μg/L) in comparison to 38/32 pts. with ferritin values surmounting 250 μg/L. Pts. with diffuse growth or cluster formation (leukemic growth) were excluded. Statistical evaluation was performed with SAS 9.1 software using Wilcoxon-Mann-Whitney tests. The results were regarded as significant if the p-value was under 5%. Both patient subgroups were balanced according to cytogenetics, age and MDS WHO-subtype. Results In the patients subgroup with normal ferritin (n=14) the numbers of BFU-E ranged between 0 and 76 (std.dev. 19.63) with a median of 3.5 and a mean of 10.7, the numbers of CFU-GM ranged between 0.5 and 38.5 (std.dev. 13.23), with a median of 6.75 and a mean of 13.2. In the patients with elevated serum ferritin (n=38) the numbers of BFU-E ranged between 0 and 250 (std.dev.40.47) with a median of 0.5 and a mean of 8.86, the numbers of CFU-GM ranged between 0 and 120 (std.dev. 29.62) with a median of 3.0 and a mean of 18.94). Statistical comparison of the numbers of BFU-E and CFU-GM between patients with normal and elevated serum ferritin yielded a highly significant difference (p=0.001348) for BFU-E and no difference for CFU-GM (p=0.570296). Conclusions Our data provide further evidence that in MDS iron overload significantly impairs bone marrow function by suppression of the burst forming activity of erythroid progenitors. If this iron is removed by adequate chelation burst forming activity might be partially restored. Myeloid progenitors do not seem to be affected by iron overload. Perspective To address the question whether chelation therapy could improve erythropoiesis we performed 4 colony assays at minimum as follow up in 32pts the analysis of which is under way. In this group 8 pts. showed a normal ferritin while 26 pts. had an elevated ferritin (> 250 μg/L). Of these, pts. 10 were treated with chelation therapy. Furthermore, 9 pts. were monitored by magnetic resonance imaging (MRT). The results of these examinations will be related to the other parameters evaluated in this study and presented in detail. Disclosures: Haase: Novartis Oncology, Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Evidence for a Suppression of the Colony Forming Capacity of Erythroid Progenitors by Iron Overload in Patients with MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2694-2694 ◽  
Author(s):  
Julia Hartmann ◽  
Ursula Sinzig ◽  
Gerald Wulf ◽  
Lorenz H. Truemper ◽  
Friederike Braulke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Peripheral Blood ◽  
Chelation Therapy ◽  
Elevated Serum ◽  
Prognostic Impact ◽  
Erythroid Progenitors ◽  
Colony Assays ◽  
Colony Forming Capacity

Abstract Introduction: In MDS transfusional iron overload is known to be related to increased morbidity mainly due to cardiac and/or hepatic damage. As a consequence an excess mortality rate in polytransfused pts. has been demonstrated. A negative prognostic impact of transfusion need has been proven as an independent marker of bad prognosis. In 1996 Jensen et al. demonstrated that an adequate chelation therapy could improve the transfusion need of pts. with MDS significantly (Br J Haematol 1996, 94, 288–299). This observation and personal communications of several more cases with improvement of transfusion need under adequate chelation therapy implies that iron overload might not only be harmful to hepatocytes and cardiomyocytes but also to bone marrow progenitor cells. Their function is intrinsically impaired by MDS itself and thus might be further affected by a “second hit” in the form of toxic iron overload which might further impair their colony forming capacity. Patients and methods: For this purpose we performed colony assays from the peripheral blood from 42 pts. with MDS (RA/RARS: n=14, RCMD/RS: 12, RAEB-I/II:10, 5q-syndrome: 3, MDS-U: 2, CMML: 1; age: 39 – 86 yrs. (median: 69 yrs.); cytogenetics: normal: 26, 5q-: 6, −7: 2, complex: 4, others: 4) with (serum ferritin ≥250 μg/L, range: 273 – 6267 μg/L) and without iron overload (range: 23 – 213 μg/L). Only pts. without hepatic and/or active infectious diseases, without chemotherapy/epigenetic therapy during the last 6 months and without cytokine and/or corticoid therapy during the last 3 months before performance of colony assays were considered. BFU-E and CFU-GM were analysed by the same person (U.S.) after 12 – 16 days in cultures from peripheral blood, performed as described (Vehmeyer K et al., Leuk Res, 2001; 25(11):955–9) in 11(BFU-E)/9 (CFU-GM) pts. with normal ferritin-values (normal range: 20–250 μg/L) in comparison to 31/26 pts. with ferritin values surmounting 250 μg/L. Pts. with diffuse growth or cluster formation (leukemic growth) were excluded. Statistical evaluation was performed with SAS 9.1 software using Wilcoxon-Mann-Whitney tests. The results were regarded as significant if the p-value was smaller than 5%. Both patients subgroups were balanced according to cytogenetics, age and MDS WHO-subtype. Results: In the patients subgroup with normal ferritin (n=11) the numbers of BFU-E ranged between 0 and 76 (std.dev. 21.96) with a median of 3.5 and a mean of 10.1, the numbers of CFU-GM ranged between 0.5 and 38.5 (std.dev. 13.99), with a median of 5.5 and a mean of 11.1. In the patients with elevated serum ferritin (n=31) the numbers of BFU-E ranged between 0 and 27 (std.dev.5.32) with a median of 0.5 and a mean of 2.35, the numbers of CFU-GM ranged between 0 and 120 (std.dev. 30.18) with a median of 3.0 and a mean of 19.33). Statistical comparison of the numbers of BFU-E and CFU-GM between patients with normal and elevated serum ferritin yielded a highly significant difference (p=0.003845) for BFU-E and no difference for CFU-GM (p=0.939728). Conclusions: Our data for the first time provide evidence that in MDS iron overload significantly impairs bone marrow function by suppression of the burst forming activity of erythroid progenitors. If this iron is removed by adequate chelation burst forming activity might be partially restored. Myeloid progenitors do not seem to be affected by iron overload.

Retrospective analysis of cytogenetic and clinical characteristics on 65 patients with multiple myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5075-5075
Author(s):  
Li Yang ◽  
Jingsong He ◽  
Xiaojian Meng ◽  
Guoqing Wei ◽  
Wenjun Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Retrospective Analysis ◽  
Clinical Features ◽  
Elevated Serum ◽  
Serum Levels ◽  
Fish Analysis ◽  
Molecular Cytogenetic ◽  
Cytogenetic Aberrations ◽  
Conventional Cytogenetics

Abstract Abstract 5075 Multiple myeloma (MM) is a malignant disorder characterized by abnormal proliferation of monoclonal, immunoglobulin producing plasma cells in the bone marrow. Studies with large samples have shown that molecular cytogenetic changes play an important role in the prognosis of MM. Based upon these findings, we tested cytogenetic aberrations of 65 patients with MM by conventional cytogenetics analysis and FISH technique in this study. Retrospective study was done on these cases for clinical features. Methods: This is a retrospective analysis of 65 patients with MM diagnosed between June 2007 and May 2010 including 13 relapsed cases and 52 newly diagnosed patients. Patients received bortezomib-based combination chemotherapy including bortezomib plus dexamethasone (BD) and the triplet combinations (bortezomib, adriamycin, dexamethasone (BAD), bortezomib, cytoxan, dexamethasone (BCD) and bortezomib, melphalan, prednisone (BMP) or traditional chemotherapy including doxorubicin, vincristine plus dexamethasone (VAD), melphalan plus dexamethasone (MP), melphalan, dexamethasone plus thalidomide (MPT)). To further clarify the correlation between cytogenetic and clinical features on patients with multiple myeloma, we used conventional cytogenetics analysis with R-banding technique and interphase fluorescence in situ hybridization (FISH) to describe the molecular cytogenetic characterization of bone marrow nucleated cells from 65 patients. SPSS (version 18.0) software was used for data analysis, χ2 tests or Fisher's exact test was used for betweengroup comparison of the discrete variables and Log- Rank was used for survival analysis. p<0.05 reflects the remarkable significance. Results: 16.9% of patients (11/65) showed abnormal cytogenetic aberrations including 90.9% (10/11) cases with ultra complex aberration and complex aberration via conventional cytogenetics. In addition, we were able to show aberrations in 49.2% (32/65) of patients by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7% (18/65), 13.8% (9/65), 16.9% (11/65), and 29.2% (19/65) by FISH, respectively. 1q21 amplification is strongly associated with 13q14 mutation (P=0.008), demonstrating significant correlation between two. Abnormality of 13q14 deletion or 1q21 amplification were associated with lower levels of albumin (P<0.05). Patients with 13q14 deletion frequently had stage III disease by DS and ISS staging, and compared with patients not detected on FISH analysis, they tended to have elevated serum levels of β2-microglobulin at diagnosis (P<0.05). 17p13 deletion coexistent with 13q14 deletion frequently correlate with elevated serum levels of β2-microglobulin and advanced clinical staging. The median progression-free survival (PFS) of patients with 17p13 deletion or 17p13/13q14 aberrations were both 11.0m, significantly lower than patients with no detected abnormality (median PFS 19.0m) (P<0.05). The median overall survival (OS) of patients with FISH negtive results was 38.0m, significantly higher than those with 13q14, 14q32 or 1q21 abnormality and 17p13/13q14 or more than three abnormalities (P<0.05). Conclusions: This study validates myeloma cells are prone to show complex aberration and FISH is superior in the detection of cytogenetic aberrations to conventional cytogenetics analysis for patients with multiple myeloma. 1q21 had significant correlation to 13q abnormality. 17p13 deletion coexist with 13q14 deletion and 14q32 rearrangeent were used to associate with poor prognosis. 17p13 deletion or 17p13/13q14 deletion was associated with poorer PFS while abnormality of 13q14, 1q21,14q32, 17p13/13q14 or more than 3 abnormalities were correlate with poorer OS. Disclosures: No relevant conflicts of interest to declare.

Hemophagocytic Syndrome Presenting as Acute Hepatic Failure in Two Infants: Clinical Overlap with Neonatal Hemochromatosis

1999 ◽  
Vol 2 (4) ◽  
pp. 360-366 ◽  
Author(s):  
Maria Parizhskaya ◽  
Jorge Reyes ◽  
Ronald Jaffe
Keyword(s):  
Bone Marrow ◽  
Liver Transplantation ◽  
Liver Failure ◽  
Serum Ferritin ◽  
Hepatic Failure ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Elevated Serum ◽  
Acute Hepatic Failure ◽  
Neonatal Hemochromatosis ◽  
Neonatal Liver

Two patients with hemophagocytic lymphohistiocytosis who presented with acute liver failure are reported. Both presented with fever, hepatosplenomegaly, markedly elevated liver function tests, abnormal coagulation profiles, and an increase in serum ferritin. Both infants were diagnosed with neonatal hemochromatosis based on a clinical picture of hepatic insufficiency with hyperferritinemia and were referred for liver transplantation. The first patient died of liver failure and septicemia before transplantation. Review of autopsy material revealed a hepatitis-like pattern and extensive infiltration of liver and other organs including bone marrow by histiocytes, some of which were hemophagocytic. The second patient underwent liver transplantation but died 44 days thereafter from progressive hemophagocytic lymphohistiocytosis. Examination of the resected liver demonstrated a hepatitis-like pattern, proliferation of histiocytes, and hemophagocytosis, and the bone marrow revealed hemophagocytic histiocytosis. Hemophagocytosis recurred in the allograft. Hepatic manifestations are common in hemophagocytic lymphohistiocytosis and overt hepatic failure may occur, but initial presentation as fulminant hepatic failure is not well recognized. Elevated serum ferritin can make the distinction from neonatal hemochromatosis and other forms of neonatal liver failure difficult. Hemophagocytic lymphohistiocytosis should be considered in the differential diagnosis of neonatal liver disease, especially when it is accompanied by cytopenias.

Comparison of Survival and Clinical Features In Different Age Cohorts of Patients with Multiple Myeloma: A Single Center Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4997-4997
Author(s):  
Jae Ho Jeong ◽  
Shinkyo Yoon ◽  
Dalyong Kim ◽  
Jeong Eun Kim ◽  
Dok Hyun Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Features ◽  
Bone Lesion ◽  
Elevated Serum ◽  
High Serum ◽  
Single Center ◽  
Age Cohorts ◽  
Β2 Microglobulin ◽  
The Impact

Abstract Abstract 4997 Purpose This analysis was aimed to compare clinical features in different age cohorts of multiple myeloma (MM) patients and to identify the impact of the clinical characteristics on survival in the patients in a single center. Patients and Methods We retrospectively analyzed data from 513 patients between Sep 1995 and Feb 2010 in the Asan Medical Center. Correlation of baseline characteristics with survival was made by the following age strata: <45, 45–54, 55–64, and ≥65 years of age. Results Median observed overall survival (OS) in the entire cohort was 3.20 years (95% confidence interval: 2.71–3.68). Observed survival decreased steadily with ages from 4.56 years in patients younger than age 45 years to 2.50 years in patients ≥65 years (P=0.003). The patients in the oldest group (age 65 years or older) were more likely to have International Staging System (ISS) stage II or III than others (P=0.007). There were no significant differences in hypercalcemia (≥10 mg/dL), elevated serum creatinine (≥2 mg/dL), anemia (Hb <10 g/dL) and osteolytic bone lesion, so called CRAB among the different age cohorts. Prognostic factors including elevated C-reactive protein (CRP) (≥ 0.8mg/dL), lactate dehydrogenase (LDH), bone marrow plasma cell infiltration also did not differ significantly among 10-year age cohorts. However, hypoalbuminemia (<3.5 g/dL) and high serum β2-microglobulin (≥3.5 mg/dL) level were more frequent in patients ≥65 years of age (P=0.001 and P=0.046, respectively). Furthermore, higher proportion of patients underwent ASCT in the younger 10-year age cohorts (71.4%, 53.7%, 43.4%, 2.5% in < 45, 45–54, 55–64, and ≥ 65 years of age, respectively, P<0.001). Conclusion No significant differences in the myeloma related organ or tissue impairment and prognostic markers including CRP, LDH and bone marrow infiltration of myeloma cells were noted among different age groups. However, survival significantly declined in the higher age group, which might be related to higher ISS stage associated with hypoalbuminemia, high serum β2-microglobulin level and lower proportion of patients receiving ASCT. Disclosures: No relevant conflicts of interest to declare.

Immunoscintigraphy in Medullary Thyroid Cancer Using an 123I- or 111ln-Labelled Monoclonal Anti-CEA Antibody Fragment

1986 ◽  
Vol 25 (06) ◽  
pp. 227-231 ◽  
Author(s):  
Chr. Eilles ◽  
W. Spiegel ◽  
W. Becker ◽  
W. Börner ◽  
Chr. Reiners
Keyword(s):  
Bone Marrow ◽  
Thyroid Cancer ◽  
Potassium Iodide ◽  
Medullary Thyroid Cancer ◽  
Elevated Serum ◽  
Antibody Fragment ◽  
Special Importance ◽  
Medullary Thyroid ◽  
Medullary Cancer ◽  
Serum Cea

The monoclonal anti-CEA F(ab’)2 fragment MAb BW 431/31, labelled with 123I or111 In, was used for immunoscintigraphy (IS) in 9 patients with medullary cancer of the thyroid (CCC). The results of 11 studies lead to the following conclusions: 1) When using radioiodine as a label for MAb in IS, potassium iodide is absolutely necessary to block the thyroid which is of special importance in patients with thyroid cancer; 2) Preinjection of “cold” MAb reduces the relatively high unspecific uptake (especially in bone marrow) of MAb BW 431/31, which is of special importance for the antibody labelled with 111 In; 3) IS with MAb BW 413/31 in patients with CCC and elevated serum CEA is positive only in cases with large secondaries; and 4) In patients with CCC and several manifestations of secondaries, only a single (large) metastasis may be apparent.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

Sign in / Sign up

Export Citation Format

Share Document