Management of granulomatosis with polyangiitis complicated by intestinal perforation and pancytopenia: a case report and literature review.

Granulomatosis with polyangiitis is a systemic vasculitis. While the classic triad typically comprises otorhinolaryngologic, pulmonary, and renal manifestations, it is essential to recognize that granulomatosis with polyangiitis can affect any organ. Furthermore, reports have documented less common sites of involvement, such as the gastrointestinal tract. In this case-based review, we focus on a case of granulomatosis with polyangiitis presenting with intestinal perforation and the added challenge of concurrent pancytopenia.A 25-year-old female was diagnosed with granulomatosis with polyangiitis, with her clinical course progressing from joint pain to severe multi-organ involvement, including gastrointestinal complications. Treatment challenges emerged with the development of pancytopenia. While this may not directly result from granulomatosis with polyangiitis, it introduced an additional layer of complexity and delayed the induction of remission with immunosuppressants. Despite initial stabilization, an unexpected jejunal perforation occurred, requiring surgical intervention and subsequent postoperative care. The case underscores the complex nature of granulomatosis with polyangiitis and its potential complications. A literature search yielded discrete relevant cases in the context of our patient's intricate presentation, which has been summarized.We highlight the complexities in diagnosing and managing granulomatosis with polyangiitis-related complications, especially in uncommon presentations, and emphasize the importance of a personalized approach to patient care in these circumstances.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

Donor-derived stem cell infusion for sustained pancytopenia after CD19 CAR-T therapy for relapsed patients post allogeneic stem cell transplantation.

OBJECTIVES: To investigate the effectiveness of donor-derived chimeric antigen receptor T (CAR-T) cells in the treatment of relapsed cases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and whether donor-derived peripheral blood stem cells (PBSCs) have a therapeutic effect on pancytopenia after CAR-T cell therapy. METHODS: We analyzed data from five adults with B-cell acute lymphoblastic leukemia (ALL) who had relapse after allo-HSCT and received donor-derived CAR-T cell therapy and donor-derived PBSCs to promote hematopoietic recovery. RESULTS: All patients had negative minimal residual disease after CAR-T therapy, grade 1-2 cytokine release syndrome, and developed grade 4 hematologic toxicity. During the pancytopenia stage after CAR-T cell therapy, donor-derived PBSCs were transfused without graft-versus-host disease (GVHD) prophylaxis. Four patients had grade I-II acute GVHD (aGVHD). After corticosteroid treatment, aGVHD resolved and hematopoiesis was restored. Although steroids in combination with etanercept and ruxolitinib relieved symptoms in one patient with grade IV aGVHD, complete hematopoietic recovery was not achieved, and the patient died due to severe infection. CONCLUSIONS: Donor-derived CAR-T cell therapy is safe and effective in patients with relapsed/refractory ALL after allo-HSCT. Donor-derived PBSCs infusion could achieve hematopoietic recovery with controllable aGVHD in patients with persistent pancytopenia.

Allogeneic hematopoietic stem cell transplantation corrects ligase IV deficiency.

BACKGROUND: Mutations in the DNA ligase IV (LIG4) gene cause a rare autosomal recessive disorder called LIG4 deficiency syndrome. The LIG4 deficiency is featured by severe disorders, including combined immunodeficiency disease, special face ("bird-head-like" face), developmental delays, pancytopenia, and radiosensitivity. Currently there are no curative treatment options except potentially by performing a hematopoietic stem cell transplantation (HSCT). CASE PRESENTATION: Here we reported the clinical course of a 4 and 1/2-year-old Chinese female with LIG4-deficiency featured with pancytopenia, severe growth retardation (weight of 13.5 kg, < 3rd percentile), length of 100 cm (<2d percentile), head circumference of 46 cm (<3rd percentile), and mild microcephaly. Despite regular IVIG administrations (5 g, once a month), the patient's thrombocytopenia had progressed. Eventually, the patient received HSCT that successfully normalized the LIG4 syndrome associated pancytopenia and corrected the LIG4 mutation. Despite progress the patient succumbed to thrombotic microangiopathy more than 3 months after HSCT. CONCLUSIONS: This case reports an example of partially successful HSCT as a treatment option for LIG4 syndrome. It is possible that individual factors influence the therapeutic effect of HSCT in LIG4 deficiency.

The journey from viral hepatitis to hypocythemia: Two case reports.

Acute viral hepatitis, including hepatitis A, B, E, D, and G, can lead to severe bone marrow suppression due to cytotoxic lymphocytes. The bone marrow suppression causes aplastic anaemia which is mostly unresponsive to immunosuppressive therapy. Such patients require bone marrow transplant for a complete cure. The pancytopenia can evolve during recovery from transaminitis. We are presenting two case reports relating aplastic anaemia with acute viral hepatitis in two young patients-23 and 16 years of age. The 23-year-old female patient had hepatitis A associated with aplastic anaemia whereas the young 16-year-old male patient was diagnosed with Hepatitis E IgG associated aplastic anaemia. Unfortunately, the first patient could not cope with the complications relating to pancytopenia and was unable to reach the bone marrow transplant stage. The second patient did not have a bone marrow transplant but showed an excellent response to immunosuppressive therapy before the transplant and survived.

Severe autoimmune pancytopenia after autologous hematopoietic stem cell transplantation for Hodgkin lymphoma.

Autoimmune pancytopenia is rarely seen with Hodgkin lymphoma, and only one pediatric case of pancytopenia after autologous hematopoietic stem cell transplantation (HSCT) has been reported. We herein report a case of autoimmune pancytopenia that developed after autologous HSCT for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). A 56-year-old Japanese woman underwent autologous HSCT for NLPHL. She developed autoimmune pancytopenia seven months after autologous HSCT. In this case, PSL was effective, and the blood cell counts normalized completely. However, the patient suffered from a fatal infection, probably because of immunosuppression caused by prolonged administration of PSL, as well as a history of several chemotherapies and autologous HSCT. To our knowledge, this is the first adult case of autoimmune pancytopenia after autologous HSCT for Hodgkin lymphoma. To further validate the optimal treatment strategy for autoimmune cytopenia after autologous HSCT, more cases are necessary.

Pancitopènia en un lactant secundària a anèmia perniciosa materna / Pancitopenia en un lactante secundaria a anemia perniciosa materna / Pancytopenia secondary to maternal pernicious anemia in an infant

Introducció. L’anèmia megaloblàstica és una causa poc freqüent de pancitopènia en lactants. La seva principal etiologia és el dèficit matern de vitamina B12 en recent nascuts alimentats exclusivament amb lactància materna, toti que en alguns casos aquest déficit pot ser secundari auna anèmia perniciosa materna.Cas clínic. Lactant de 3 mesos que va consultar a urgènciesper vòmits i estancament ponderal de 3 setmanesd’evolució. En l’analítica sanguínia destacava anèmia (hemoglobina 6,5 g/dL), trombocitopènia (12 x10E9/L) i leucopènia (5,5 x10E9/L) amb neutropènia severa (0,11x10E9/L). Els nivells de vitamina B12 van resultar ser de60 pg/mL. Davant la confirmació d’anèmia megaloblàstica,es completà l’estudi amb una analítica sanguínia i gastroscòpia materna que mostraren una anèmia perniciosa, prèviament desconeguda, causant del dèficit de cobalamina ala pacient. Es va iniciar suplementació amb vitamina B12endovenosa, comprovant-se bona resposta reticulocitària,augment de leucòcits i manteniment de xifra normal deplaquetes i hemoglobina.Comentaris. Les alteracions neurològiques secundàries aldéficit de vitamina B12 poden arribar a ser severes, i enalgunes ocasions fins i tot irreversibles. La importància delseu diagnòstic és la instauració de suplementació precoçper a corregir el dèficit i així millorar el pronòstic. (AU)

Introducción. La anemia megaloblástica es una causa poco frecuente de pancitopenia en lactantes. Su principal etiología es eldéficit materno de vitamina B12 en recién nacidos alimentadosexclusivamente con lactancia materna, aunque en algunos casospuede ser secundario a una anemia perniciosa materna.Caso clínico. Lactante de 3 meses que consultó a urgencias porvómitos y estancamiento ponderal de 3 semanas de evolución. Enla analítica sanguínea destacaba anemia (hemoglobina 6,5 g/dL), trombocitopenia (12 x10E9/L) y leucopenia (5,5 x10E9/L) con neutropenia severa (0,11 x10E9/L). Los niveles de vitamina B12 resultaron ser de 60 pg/mL. Ante la confirmación de anemia megaloblástica, se completó el estudio con una analítica sanguínea ygastroscopia materna que mostraron una anemia perniciosa, previamente desconocida, causante del déficit de cobalamina a la paciente. Se inició suplementación con vitamina B12 endovenosa,comprobándose buena respuesta reticulocitaria, aumento de leucocitos y mantenimiento de cifra normal de plaquetas y hemoglobina.Comentarios. Las alteraciones neurológicas secundarias al déficitpueden llegar a ser severas, y en algunas ocasiones incluso irreversibles. La importancia de su diagnóstico es la instauración de suplementación precoz para corregir el déficit y así mejorar el pronóstico. (AU)

Introduction. Megaloblastic anemia is a rare cause of pancytopeniain infants. Its main etiology is maternal vitamin B12 deficiency inexclusively breastfed newborns, although in some cases it may besecondary to maternal pernicious anemia.Case report. Three-month-old infant who consulted the emergencydepartment for vomiting and a three-week failure to thrive. Laboratory evaluation was significant for anemia (hemoglobin 6,5 g/dL),thrombocytopenia (12 x109/L) and leukopenia (5,5 x109/L) withsevere neutropenia (0,11 x109/L). Vitamin B12 levels were foundto be 60 pg/mL. Upon confirmation of megaloblastic anemia, thestudy was completed with a blood test and maternal gastroscopythat showed a previously unknown pernicious anemia causingthe patient's cobalamin deficit. Vitamin B12 supplementationwas started intravenously, proving good reticulocyte response,increase of leukocytes and normalization of platelet and hemoglobin values.Comments. Neurological alterations secondary to vitamin B12 deficit can be severe, and sometimes even irreversible. The importance of its diagnosis is the establishment of early supplementation to correct the deficit and thus improve the prognosis. (AU)

[A Case of Effective Plasma Exchange for Thrombotic Microangiopathy during Chemotherapy for Pancreatic Cancer].

The patient was a 78-year-old man. After 4 courses of GEM plus nab-PTX therapy for multiple recurrent liver metastases after pancreatic body cancer surgery, the patient was aware of general malaise and edema of the extremities. Blood tests showed pancytopenia, and he was admitted to the hospital with a diagnosis of chemotherapy-induced pancytopenia. On the second day, hemolytic anemia with crushed red blood cells was observed, suggesting thrombotic microangiopathy (TMA). Considering the possibility of thrombotic thrombocytopenic purpura(TTP), the patient was started on plasma exchange with steroids. After 7 days of plasma exchange, his thrombocytopenia, hemolytic anemia, and renal dysfunction improved, and he was discharged from the hospital on the 28th day. Although GEM-induced TMA is a life-threatening complication, there is no established treatment for it. We report a case of GEM-induced TMA that was successfully treated with plasma exchange.

When are idiopathic and clonal cytopenias of unknown significance (ICUS or CCUS)?

Rapid advances in sequencing technology have led to the identification of somatic mutations that predispose a significant subset of the aging population to myeloid malignancies. Recently recognized myeloid precursor conditions include clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS). These conditions can present diagnostic challenges and produce unwarranted anxiety in some instances. While the risk of progression to myeloid malignancies is very low in CHIP, true CCUS confers an exponential increase in risk. Idiopathic cytopenia of unknown significance (IDUS) lacks the predisposing genetic mutations and has a variable course. In this review we define the early myeloid precursor conditions and their risk of progression. We present our diagnostic approach to patients with unexplained cytopenias and discuss the clinical consequences of CHIP and CCUS.

Autoimmune pancytopenia after liver transplantation: A case report.

INTRODUCTION: Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and autoimmune neutropenia (AIN) are reported in the literature after liver, intestinal, heart, pancreas, and kidney transplants. We report a case of autoimmune pancytopenia (AIHA, AIN and ITP) 9 years after liver transplantation with confirmed erythrocyte and neutrophil auto-antibodies. CASE REPORT: A 49 years old man was admitted to our hospital presented with dysentery and fever, with history of liver transplantation in 2008. Laboratory evaluation demonstrated hemoglobin: 7.2 g/dL, granulocytes: 0.10 × 109/L and platelets: 15 × 109/mm³; indirect bilirubin: 3.62 mg/dL; lactate dehydrogenase: 603 U/L. Direct antiglobulin test revealed a monospecific anti-IgG plus C3 and the acid eluate was reactive to all panel red cells, consistent with an AIHA. Granulocyte immunofluorescence test (GIFT) and agglutination test (GAT) were reactive for granulocytes. Test with Luminex technology for human neutrophil antigen (HNA) antibody detection was strong reactive with beads expressing HNA-1a, -1b, -1c, -2, -4a and -5a antigens. HNA genotyping revealed the presence of the corresponding antigens, confirming the autoantibodies. Test with Luminex technology for human leucocyte antigen (HLA) antibody detection was negative. Monoclonal antibody immobilization of platelet antigens (MAIPA) assay was negative. Viral causes were excluded. The condition was compatible with clinical onset of autoimmune pancytopenia. Prednisone was administered at an initial dose of 1 mg/kg/day and immunosuppressive therapy was adjusted. This treatment resulted in rapid resolution of pancytopenia. CONCLUSION: Combined autoimmune pancytopenia (AIHA, AIN and ITP) is a rare condition that may occur after liver transplantation. Early recognition of this phenomenon permits appropriate treatment.

Management of COVID-19 infection in organic acidemias.

The COVID-19 pandemic has affected the health and healthcare of individuals of all ages worldwide. There have been multiple reports and reviews documenting a milder effect and decreased morbidity and mortality in the pediatric population, but there have only been a small number of reports discussing the SARS-CoV-2 infection in the setting of an inborn error of metabolism (IEM). Here, we report two patients with underlying metabolic disorders, propionic acidemia and glutaric aciduria type 1, and discuss their clinical presentation, as well as their infectious and metabolic management. Our report demonstrates that individuals with an underlying IEM are at risk of metabolic decompensation in the setting of a COVID-19 infection. The SARS-CoV-2 virus does not appear to cause a more severe metabolic deterioration than is typical.

A coronavirus disease-2019 induced pancytopenia.

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) pandemic progresses, various hematologic complications have emerged, often centered around the hypercoagulable state. However, pancytopenia represents a rare but serious complication from SARS-CoV2 infection. While lymphopenia is a common finding, concomitant acute anemia and thrombocytopenia are not commonly reported. We describe a novel case of SARS-CoV2 pancytopenia in a 40-year-old male without active risk factors for cell line derangements but subsequent critical illness.

Hyperpigmentation, severe alopecia, and six days of instability in a case of severe methotrexate hypersensitivity reaction.

INTRODUCTION: Ectopic pregnancy (EP) is an emergency condition in the gynecologic field. Methotrexate (MTX) is a drug of choice for the medical treatment of EP. Severe adverse events are rare among patients treated with MTX for this condition. REASON FOR REPORT: We describe a woman with severe multi-organ involvement experiencing about six days of instability after treatment with just a single-dose MTX for EP. This life-threatening condition is not common with a single dose of MTX. A 30-year-old healthy woman was treated medically with MTX for an EP. Three days later the patient was admitted to the emergency department of our hospital with generalized pustular rashes, alopecia, hyperpigmentation, nausea and vomiting, oral ulcers, and raised Creatinine level. Four days later due to pancytopenia, fever, and loss of consciousness, she was transferred to the intensive care unit and was intubated. OUTCOME: After 38 days of hospitalization, treatment was successful with leucovorin and supportive care and the patient's symptoms and clinical manifestations were regressed.

Common Variable Immunodeficiency, Autoimmune Hemolytic Anemia, and Pancytopenia Associated With a Defect in IKAROS.

OBJECTIVE: Mutations in IKZF1, which encodes Ikaros family zinc finger 1 (IKAROS) transcription factor, are associated with recurrent infections, cytopenia, autoimmune diseases, and hematologic malignancies. Diverse clinical phenotypes resulting from IKZF1 mutations include pulmonary fungal infections, cytopenia, autoimmune hemolytic anemia (AIHA), and malignancies. In this study, we aimed to assess the DNA-binding ability and pericentromeric (PC) localization of a variant of IKZF discovered in a patient. MATERIALS AND METHODS: DNA-binding ability of a pathogenic IKZF variant was tested using electrophoretic mobility shift assay and PC localization of the variant was assessed by immunofluorescent microscopy in NIH3T3 cells. RESULTS: Clinical features of a 3-month-old male infant who underwent hematopoietic stem cell transplantation because of an IKZF1 mutation-associated common variable immunodeficiency, AIHA, and pancytopenia are described. DNA studies revealed a heterozygous missense variant (IKZF1 NM_006060 c.427C>T; p.R143W). Cotransfection studies revealed that mutant R143W has a partial dominant-negative effect over PC targeting and DNA binding. CONCLUSIONS: IKZF1 mutation must be kept in mind if neonatal AIHA, common variable immunodeficiency, and pancytopenia are observed.

Autoimmune cytopenia in chronic lymphocytic leukemia: diagnosis and treatment.

The aim of the study was to determine peculiarities of the distribution, diagnosis and development of immune cytopenias in patients with chronic lymphocytic leukemia (CLL) and to evaluate the efficacy of the different therapeutic approaches. MATERIALS AND METHODS: Treatment response and survival of 83 patients with CLL complicated by immune cytopenia (IC) were analyzed. Treatment schedules in 58 medicated patients included corticosteroids; chemotherapy (COP, CHOP regimens), immunotherapy (rituximab alone), immunochemotherapy (rituximab-containing regimens - R-COP, R-CHOP). Twenty-five patients underwent splenectomy. RESULTS: The use of corticosteroids, as the first line of treatment, resulted in short-term remission in most patients. Chemotherapy was effective in a half of CLL patients, but duration of the remission did not exceed 32 months in CLL associated with autoimmune hemolytic anemia and immune thrombocytopenia. After rituximab monotherapy (10 patients) the stable remission was reached in 60% of the patients with median relapse-free survival of 40 months. Rituximab containing chemotherapy (22 patients) caused the long-term remission in 72% of the patients with median relapse-free survival of 76 months. Splenectomy performed in 25 patients with CLL complicated by IC was effective in 70% of the patients. The outcome of splenectomy depends on IC entity. The best response was registered in associated immune thrombocytopenia (median overall survival 118 months), the worst - in Fisher - Evans syndrome (15 months). CONCLUSIONS: The treatment of patients with CLL complicated by ICs should be individualized. For CLL patients without significant enlargement of lymph nodes and spleen, low lymphocytosis, associated with autoimmune hemolytic anemia or immune thrombocytopenia, the monotherapy with rituximab is optimal. In case of occurrence of autoimmune hemolytic anemia, immune thrombocytopenia or Fisher - Evans syndrome in CLL patients with enlargement of lymph nodes, spleen, significant lymphocytosis, the use of R-COP or R-CHOP schemes, 4-6 courses, is the most effective. Splenectomy is indicated in patients with massive splenomegaly, the resistance to medication, recurrent relapses after adequate therapy.

[CD34+ cell selection methods, quality controls and expected results: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Procédé de préparation, contrôles de qualité et spécifications des immunosélections CD34+ : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

CD34+ immunomagnetic positive selection allows for CD34+ hematopoietic progenitors separation from CD3+ lymphocytes subsets, usually from an apheresis product collected from a previously mobilized donor. This T-cell depleted stem cell graft is primarily intended for rare cases (around 2% of allotransplanted patients in France) of severe, persistent, symptomatic bi- or tri-cytopenia post-allotransplantation, in order to allow for hematologic reconstitution without increasing the risk of GvHD occurrence. Although semi-manual and complex, the process is of sufficient robustness to consistently generate a cellular product with distinctive features and specifications, based on iterative in-process quality controls, that are discussed within these guidelines.

Autoimmune pancytopenia occurring late after simultaneous pancreas and kidney transplantation.

A 35-year-old woman presented with a widespread petechial rash and pancytopenia. She underwent simultaneous pancreas and kidney transplantation for type 1 diabetes 8 years previously followed by a renal transplant 1 year prior to presentation, and was taking tacrolimus as long-term immunosuppression. The full blood count showed haemoglobin 97 g/L, platelet count 2×109/L and neutrophil count 0.22×109/L. Peripheral blood film examination confirmed genuine thrombocytopenia in the absence of any haemolytic or malignant features. Serological testing identified autoantibodies against all three blood lineages, consistent with a diagnosis of autoimmune pancytopenia. Treatment with steroids, intravenous immunoglobulins, romiplostim and mycophenolate mofetil achieved only fleeting remissions. Blood counts eventually normalised following the administration of rituximab and a change from tacrolimus to ciclosporin immunosuppression. Cytopenias are a well-recognised complication of post-transplantation care but we believe this to be the first reported case of autoimmune pancytopenia following solid organ transplantation. In this case report, we discuss the approach to investigation of haematological abnormalities post-transplant and the rationale for, and outcome of, the management of this rare case.