Hemophagocytic Lymphohistiocytosis: Single-Center Series of 12 Cases from Saudi Arabia

Clinical Medicine Insights Pediatrics ◽

10.4137/cmped.s35853 ◽

2016 ◽

Vol 10 ◽

pp. CMPed.S35853 ◽

Cited By ~ 3

Author(s):

Ghaleb Elyamany ◽

Azzah Alzahrani ◽

Huda Elfaraidi ◽

Omar Alsuhaibani ◽

Nada Othman ◽

...

Keyword(s):

Saudi Arabia ◽

Hemophagocytic Lymphohistiocytosis ◽

Mutational Analysis ◽

Age Of Onset ◽

Positive Family History ◽

Case Series ◽

Cell Transplant ◽

First Case ◽

Response To Chemotherapy ◽

Female Predominance

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease that commonly appears in infancy, although it has been reported in adults. Chemoimmunotherapy-based treatments have improved the survival of patients with HLH; however, overall survival is still poor. We retrospectively analyzed the data of 12 HLH patients who were admitted between 2005 and 2014. All patients were Saudi Arabia in origin with a female predominance (75%) and a median age of onset of 9.5 months. The consanguinity rates were significantly high (75%) with a positive family history in 41% of cases. Of the 12 patients, nine were defined as primary HLH patients and three were confirmed to be secondary HLH patients. All patients fulfilled the 2004 diagnostic criteria for HLH and received HLH-2004 treatment. Six of these patients showed a good response to chemotherapy, while the remainder of the patients showed partial or no response to chemotherapy. Five patients in this cohort received stem cell transplant, and these patients are currently in remission. The mortality rate of this cohort is currently 50%. Genetic mutational analysis showed a positive STX11 mutation in five patients and a PRF1 ( perforin) mutation in two patients. To the best of our knowledge, this is the first case series of HLH from Saudi Arabia.

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Cost Effectiveness of Rituximab Maintenance (R-Maint) vs Autologous Stem Cell Transplant (ASCT) from a UK National Health Service (NHS) Perspective.

Blood ◽

10.1182/blood.v110.11.3321.3321 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3321-3321

Author(s):

Douglas R. Millar ◽

Gavin Lewis ◽

Robert Marcus

Keyword(s):

Overall Survival ◽

Cost Effectiveness ◽

Follicular Lymphoma ◽

Incremental Cost ◽

Cost Minimization ◽

Indirect Comparison ◽

Case Series ◽

Cell Transplant ◽

Response To Chemotherapy ◽

Time Point

Abstract Objectives: Both ASCT and R-Maint have been shown to be effective therapies for treating rituximab naïve patients with relapsed/refractory follicular lymphoma. The aim of this research was to assess the cost effectiveness of ASCT compared to R-Maint in this patient population (following a response to chemotherapy induction) from a UK perspective. Methods: A literature review of randomised control trials (RCTs) and case series studies suitable for comparing the efficacy of the two treatments in relapsed / refractory follicular lymphoma patients was performed. Given the heterogeneity of relevant study outcomes and designs a naïve indirect comparison was performed. Equivalent efficacy between the two therapies was assumed based upon the indirect comparison; hence a cost minimization approach was utilized. The starting time point of the analysis was following 3 cycles of CHOP therapy. In the EORTC 20981 trial both RCHOP and CHOP induction therapies were used; to reduce heterogeneity between the trial populations being compared, only results from patients who received CHOP induction in this trial were considered. Drug, administration, adverse event, and monitoring costs were evaluated from the start of treatment to the point of relapse after which time-point cost equivalence was assumed between the two therapies. Resource use and unit costs were sourced from published NHS reference costs, the EORTC 20981 study, and clinical expert opinion. Uncertainty around the assumption of equal efficacy was explored using threshold analysis based on an assumed incremental cost effectiveness ratio (ICER) threshold of £30,000 and an average utility score of 0.71 for patients with follicular lymphoma (derived from the literature). Results: One RCT and 6 case series for ASCT and one RCT for R-Maint were identified. The estimated cost of R-Maint and ASCT was £12,275 and £25,563 respectively, resulting in an estimated incremental cost of ASCT over R-Maint of £13,288 per patient. ASCT would have to offer an additional 7.5 months of overall survival to be considered cost effective compared to R-Maint. Conclusions: There is a high degree of certainty that ASCT produces higher costs compared to R-Maint, however it is uncertain whether ASCT offers an increase in either progression-free or overall survival over R-Maint in rituximab naïve patients. Consequently R-Maint may be considered a cost-saving treatment option for such patients in the treatment of relapsed/refractory follicular lymphoma patients compared to ASCT.

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Pediatric invasive disease due to Haemophilus influenzae serogroup A in Riyadh, Saudi Arabia: case series

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6687 ◽

2016 ◽

Vol 10 (05) ◽

pp. 528-532 ◽

Cited By ~ 2

Author(s):

Zailaie Roaa ◽

Alawfi Abdulsalam ◽

Ghazi Shahid ◽

Baba Kamaldeen ◽

Al Fawaz Tariq

Keyword(s):

Saudi Arabia ◽

Blood Culture ◽

Haemophilus Influenzae ◽

Vaccine Development ◽

Good Condition ◽

Case Series ◽

Invasive Disease ◽

Medical Illness ◽

Serotype A ◽

First Case

We describe the first two cases of invasive disease caused by Haemophilus influenzae serotype A in Saudi Arabia. This is the first known reported invasive Haemophilus influenzae serotype A from Saudi Arabia. Case presentation: A ten-month-old and three-month-old male not known to have any past history of any medical illness and who had received H. influenzae type b (Hib) vaccine presented to our hospital mainly with fever of few days’ duration. A provisional diagnosis of meningitis with sepsis was made and laboratory tests were requested. The chest radiograph was normal. The laboratory results revealed leukocytosis, but leukopenia was noticed in the younger infant. Blood culture and cerebrospinal fluid specimens yielded a pure culture of Haemophilus influenzae and serotyping showed the isolates to be serogroup A. Both patients were started on vancomycin and third-generation cephalosporin. On receiving the blood culture result, vancomycin was stopped. Fever subsided after 48 hours, while in the second case, it continued for 12 days from the admission date. The repeat blood cultures were negative. Antibiotic therapy was given for 10 days for the first case with an unremarkable hospital course, while the second case was complicated by seizure and received a longer duration of antibiotics. Both infants were discharged home in good condition. Conclusions: Invasive non-typeable H. influenzae strains are emerging and there is a need for surveillance of this disease. This has implications in future vaccine development.

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Patern of Acquired Hemophilia in Saudi Arabia

Blood ◽

10.1182/blood.v128.22.4987.4987 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4987-4987

Author(s):

Abdul Kareem M Al-Momen ◽

Tarek M Owaidah ◽

Zaidi Z Sayed ◽

Mady F Ahmed ◽

Hanbali Amr ◽

...

Keyword(s):

Saudi Arabia ◽

Factor Viii ◽

Case Series ◽

Factor Viii Inhibitor ◽

Acquired Hemophilia ◽

Factor Viii Level ◽

Female Predominance ◽

Viii Level ◽

Viii Inhibitor ◽

Inhibitor Titer

Abstract Background: Acquired Hemophilia (AH) is a rare bleeding disorder that develops secondary to an autoantibody against Factor VIII in persons who are not known to have any previous bleeding disorder. Aim: The aimof this retrospective case review is to explore the pattern of confirmed cases of AH that were managed in Saudi Arabia over a 5 years' period. Patients and Methods: We reviewed the charts of documented cases of AH that were managed in 5 Tertiary Hospitals (4 in Riyadh and 1 in Al Madinah Al Monawarah) from 2010 to 2014. All cases underwent medical history, physical examination, laboratory tests including complete blood count, activated partial thromboplastin time (PTT), mixing studies, factor VIII level, and Factor VIII Inhibitor titer. All patients received standard treatment. Results: We found 19 cases, but we could obtain data only for 13 cases, 4 males and 9 females, median age was 30 years (range 20-85). Risk factors were pregnancy in 5, Autoimmune disease in 2, Cancer in 1, Clopedogril in 1 and 4 were idiopathic. All cases presented with various degrees of bruises. in addition, 4 cases presented with menorrhagia, 4 cases with soft tissue hematomas, and 2 cases with gross hematuria. All cases had prolonged aPTT, which was only partially corrected with mixing studies, very low factor VIII level (median 1, range <1-12.5%), and high factor VIII inhibitor titer (median 22.4 BU, range 3.5-1932). Treatment included steroids, cyclophosphamide, immunoglobulins and Rituximab. There were 9 remissions (with 2 relapses, which responded to treatment), 2 partial responses, and 2 deaths due to massive blood loss (Hematuria). Discussion: Our case series indicates only severe AH, because many milder cases are underdiagnosed or misdiagnosed. Although the number of our cases are small, they indicate a different pattern from the published studies, because of younger age group and female predominance. Conclusion: Our case series indicates that most of our cases are young adults, with female predominance. A comprehensive review of cases from other hospitals is underway Disclosures No relevant conflicts of interest to declare.

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Hemophagocytic Lymphohistiocytosis during the Postpartum Stage of Pregnancy: A Report of Eight Cases

Acta Haematologica ◽

10.1159/000493879 ◽

2018 ◽

Vol 141 (1) ◽

pp. 55-60 ◽

Cited By ~ 1

Author(s):

Yue Song ◽

Jing-Shi Wang ◽

Yi-Ni Wang ◽

Zhao Wang

Keyword(s):

Clinical Features ◽

Liver Dysfunction ◽

Hemophagocytic Lymphohistiocytosis ◽

Standard Therapy ◽

Case Series ◽

Clinical Syndrome ◽

Haemophagocytic Lymphohistiocytosis ◽

First Case ◽

Before And After ◽

Almost All

Haemophagocytic lymphohistiocytosis (HLH) is a rare and severe clinical syndrome that can be classified as either primary or secondary. Secondary HLH can be triggered by a variety of diseases. Pregnancy-related HLH has already been observed clinically. However, most of these cases occur during pregnancy. Considering that the periods before and after delivery have different clinical features, we presented the first case series of HLH that presented during the postpartum stage of pregnancy. From these cases, we concluded that postpartum HLH is a common form of pregnancy-related HLH. Patients with postpartum HLH may suffer more complicated pathogenesis. Cytopenia was not as common as in other types of HLH, but liver dysfunction was present in almost all cases. The standard therapy of HLH-94/04 was very effective, and the outcomes of postpartum HLH were better.

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Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature

Clinics and Practice ◽

10.3390/clinpract11030062 ◽

2021 ◽

Vol 11 (3) ◽

pp. 467-471

Author(s):

Nedal Bukhari ◽

Abdulraheem Alshangiti ◽

Emad Tashkandi ◽

Mohammed Algarni ◽

Humaid O. Al-Shamsi ◽

...

Keyword(s):

Colorectal Cancer ◽

Saudi Arabia ◽

Standard Dose ◽

Dihydropyrimidine Dehydrogenase ◽

Case Series ◽

Gene Sequencing ◽

Review Of The Literature ◽

Dpyd Gene ◽

First Case ◽

Arabian Population

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report cases from our institute with colorectal cancer who experienced severe toxicities to standard dose 5-FU based chemotherapy. DPYD gene sequencing revealed rare different polymorphisms that prompted dose adjustments of administered 5-FU and capecitabine. To our knowledge, this is the first case series looking at DPYD polymorphisms in the Saudi Arabian population.

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The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India

Frontiers in Immunology ◽

10.3389/fimmu.2021.612583 ◽

2021 ◽

Vol 12 ◽

Author(s):

Snehal Shabrish ◽

Madhura Kelkar ◽

Reetika Malik Yadav ◽

Umair Ahmed Bargir ◽

Maya Gupta ◽

...

Keyword(s):

Flow Cytometry ◽

Hemophagocytic Lymphohistiocytosis ◽

Indian Population ◽

Mutational Analysis ◽

Age Of Onset ◽

Limited Information ◽

Novel Variants ◽

Current Scenario ◽

Diagnosis And Classification

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.

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Idiopathic hemophagocytic lymphohistiocytosis during pregnancy treated with steroids

Hematology Reports ◽

10.4081/hr.2015.6100 ◽

2015 ◽

Vol 7 (3) ◽

Cited By ~ 12

Author(s):

Bachar Samra ◽

Mohamad Yasmin ◽

Sami Arnaout ◽

Jacques Azzi

Keyword(s):

Pregnant Woman ◽

Hemophagocytic Lymphohistiocytosis ◽

Unknown Origin ◽

Signs And Symptoms ◽

Clinical Syndrome ◽

Cell Transplant ◽

Laboratory Findings ◽

Hematopoietic Stem ◽

First Case ◽

Variable Clinical Presentation

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe clinical syndrome characterized by a dysregulated hyperinflammatory immune response. The diagnosis of HLH during pregnancy is especially challenging due to the rarity of this condition. The highly variable clinical presentation, laboratory findings, and associated diagnoses accompanying this syndrome further complicate the problem. A pronounced hyperferritinemia in the setting of systemic signs and symptoms along with a negative infectious and rheumatological workup should raise suspicions for HLH. While treatment ideally consists of immunosuppressive chemotherapy and hematopoietic stem cell transplant, the potential toxicity to both the pregnant woman and the fetus poses a challenging decision. We report the first case of idiopathic HLH presenting as fever of unknown origin in a pregnant woman successfully treated with steroids.

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Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients With RAG1/2 Mutations: First Cases Series From Mexico and Description of Two Novel Mutations.

10.21203/rs.3.rs-202390/v1 ◽

2021 ◽

Author(s):

Mario Ernesto Cruz-Munoz ◽

Saul Oswaldo Lugo-Reyes ◽

Nina Pastor ◽

Edith González-Serrano ◽

Marco Yamazaki-Nakashimada ◽

...

Keyword(s):

Mutational Analysis ◽

Severe Combined Immunodeficiency ◽

Clinical Manifestations ◽

Case Series ◽

Missense Mutations ◽

Antigen Receptors ◽

Novel Mutations ◽

Nonsense Mutations ◽

First Case ◽

Immunological Phenotype

Abstract Mutations in Recombinase Activating Genes 1 and 2 (RAG1/2) results in human severe combined immunodeficiency (SCID). The products of these genes, are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Nonsense mutations in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with missense mutations may develop leaky SCID or Omenn syndrome (OS). A group of non-previously recognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two previously unidentified variants as causative of pathological manifestations associated to immunodeficiency. This study represents the first case series of RAG1 or RAG2 deficient patients from Mexico and Latin America.

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