Microvascular remodeling and capillary repopulation can occur after autologous hematopoietic stem cell transplant (HSCT) in patients with systemic sclerosis and systemic lupus erythematosus (SLE). We aim to report evidence for microvascular remodeling after autologous HSCT as observed by nailfold videocapillaroscopy (NVC). We describe a rare occurrence of features consistent with systemic sclerosis and SLE in a 33-year-old female with a complex clinical course refractory to conventional treatments, ultimately requiring autologous HSCT. We performed NVC before and after HSCT using optical video and light microscopy. At the microvascular level, morphologic changes in the capillary vascular bed were observed after HSCT. Pretransplant damage in capillary structure was noted as evidenced on NVC with architectural loss, ramifications, capillary drop, and decreased density. Posttransplant NVC revealed an increase in capillary density with evidence of microvascular remodeling. Further studies on the clinical use and impact of microvascular remodeling on disease progression are needed and looking into the application of NVC scoring to assess clinical response would be meaningful.

BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification.
METHODS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6.
CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.

Chronic granulomatous disease (CGD) is a rare inborn error of immunity characterized by recurrent fungal and bacterial infections due to defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. This case report describes an 11-month-old female who was initially diagnosed with tubercular lymphadenitis and presented with fever and bilateral neck swelling. Despite receiving anti-tubercular treatment (ATT) and intravenous antibiotics, the patient experienced recurrent infections and abscesses, prompting further investigation. Laboratory tests revealed normal immunoglobulin levels but abnormal nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) tests, indicating CGD. Genetic analysis (clinical exome by next-generation sequencing) confirmed a novel NCF2 gene mutation associated with autosomal recessive CGD. This patient was treated with prophylactic antibiotics and antifungals and subsequently underwent successful hematopoietic stem cell transplantation (HSCT). This highlights the diagnostic challenges associated with CGD, particularly in tuberculosis-endemic regions such as India, emphasizing the importance of considering primary immunodeficiency disorders in patients with recurrent infections. Early diagnosis and appropriate treatment, including HSCT, can significantly improve patient outcomes. The patient remained infection-free on prophylactic antimicrobials for 1.5 years post-discharge, demonstrating the potential for a favorable prognosis with timely intervention and comprehensive management.

Given the high mortality rate of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) recipients, vaccination is recommended. These recipients respond to most vaccines; however, their immune response is typically weaker during the first months or years after transplantation, compared with that of healthy individuals. Here, we report a case of IPD with serotype 3 pneumonia and empyema in an HSCT recipient who had received three doses of the 13-valent pneumococcal conjugate vaccine (PCV) and one dose of the 23-valent pneumococcal polysaccharide vaccine; furthermore, the recipient had no relapse, graft-versus-host disease, or use of immunosuppressive agents after allogeneic HSCT for acute myeloid leukemia. Moreover, we discussed the characteristics of serotype 3 Streptococcus pneumoniae, a case series of breakthrough infections with S. pneumoniae in HSCT recipients who received pneumococcal vaccines, and the potential implications for the upcoming PCV15 and PCV20 vaccines for serotype 3.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis and management. Described as primary HLH secondary to genetic defects or more commonly secondary to infections, it can also occur secondary to malignancy, i.e., malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH). A five-year-old male child presented with left cervical adenopathy and a high-spiking fever for two weeks. He had pallor, anasarca, multiple enlarged and matted cervical lymph nodes, respiratory distress, and hepatomegaly. He had continuous high-grade fever spikes (maximum 105 °F), not touching baseline despite broad-spectrum antibiotics. The CBC revealed anemia with thrombocytopenia. Liver function tests showed mild transaminitis and hypoalbuminemia. The HLH workup showed elevated ferritin, low fibrinogen, and elevated triglycerides. Lymph node biopsy showed intermediate to large atypical monomorphic lymphocyte cells with ALK, CD30, CD5, CD3, CD45, and BCL-2 (weak positive) positivity and Ki-67-95%, suggestive of anaplastic large cell lymphoma (ALCL). The bone marrow aspiration showed reactive marrow with hemophagocytosis. The patient was started on dexamethasone and chemotherapy per the Children\'s Oncology Group\'s (COG) ALCL protocol. He showed remarkable clinical improvement and went into remission after the induction phase. Malignancy associated with HLH can mimic infection, as in our patient with high-spiking fever, consolidation, and mediastinal adenopathy. A high index of suspicion is necessary to arrive at an appropriate, early diagnosis, and workup for malignancy is to be considered when an infectious etiology is not identified after thorough evaluation.

Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

Takayasu arteritis (TA) is a large-vessel vasculitis that rarely presents in infancy. Casitas B-lineage lymphoma (CBL) syndrome is a rare genetic disorder due to heterozygous CBL gene germline pathogenic variants that is characterized by a predisposition to develop juvenile myelomonocytic leukemia (JMML). Vasculitis, including TA, has been reported in several patients. Herein, we describe a patient with CBL syndrome, JMML, and TA, developing long-term remission of this vasculitis after allogeneic hematopoietic stem cell transplant (HSCT), and perform a literature review of CBL syndrome with vasculitis or vasculopathy. We report a female patient with growth delay, developmental issues, and congenital heart disease who was admitted at 14 months of age with massive splenomegaly, lymphadenopathy, fever, and hypertension. Body imaging studies revealed arterial stenosis and wall inflammation of the aorta and multiple thoracic and abdominal branches. Whole exome sequencing revealed a pathogenic variant in CBL with loss of heterozygosity in blood cells, diagnosing CBL syndrome, complicated by JMML and TA. Allogeneic HSCT induced remission of JMML and TA, permitting discontinuation of immunosuppression after 12 months. Six years later, her TA is in complete remission off therapy. A literature review identified 18 additional cases of CBL syndrome with vasculitis or vasculopathy. The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.

Due to their immunocompromised state, recipients of hematopoietic stem cell transplants (HSCTs) are at a higher risk of opportunistic infections, such as that of toxoplasmosis. Toxoplasmosis is a rare but mortal infection that can cause severe neurological symptoms, including confusion. In immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS), toxoplasmosis can cause movement disorders, including hemichorea-hemiballismus. We present the case of a 54-year-old Caucasian male with a history of hypertension and JAK-2-negative primary myelofibrosis who underwent an allogeneic peripheral blood stem cell transplant from a related donor. After the development of acute changes in mental status, left-sided weakness, and left-sided hemichorea-hemiballismus post-transplant, the patient was readmitted to the hospital. Subsequent testing included an magnetic resonance imaging (MRI) of the brain, which revealed multiple ring-enhancing lesions around the thalami and basal ganglia, as well as a cerebrospinal fluid tap that tested positive for toxoplasmosis. The patient was initially treated with intravenous clindamycin and oral pyrimethamine with leucovorin. The completion of treatment improved the patient\'s mental status but did not improve his hemichorea-hemiballismus. This case illustrates an uncommon complication associated with central nervous system (CNS) toxoplasmosis in stem cell transplant recipients. Due to its rarity, cerebral toxoplasmosis in immunocompromised patients often remains undetected, particularly in HSCT patients who are immunosuppressed to improve engraftment. Neurological and neuropsychiatric symptoms due to toxoplasmosis may be misidentified as psychiatric morbidities, delaying appropriate treatment. Polymerase chain reaction (PCR) assays offer methods that are sensitive and specific to detecting toxoplasmosis and provide opportunities for early intervention.

BACKGROUND: This article presents a case study of two white male siblings of 24 and 31 years of age of self-reported Ukrainian ethnicity diagnosed with adrenomyeloneuropathy (AMN) associated with a novel splice site mutation in the ABCD1 gene. AMN represents a form of X-linked adrenoleukodystrophy (X-ALD) characterized by demyelination of the spinal cord and peripheral nerves. The case also presents the first adult haematopoietic stem cell transplant (HSCT) for adrenomyeloneuropathy in Ukraine. The rarity of this mutation and its cerebral involvement and the treatment make this case noteworthy and underscore the significance of reporting it to contribute to the existing medical knowledge.
METHODS: The patients of 24 and 31 years initially exhibited progressive gait disturbance, lower extremity pain, and urinary incontinence, with the older sibling experiencing more advanced symptoms of speech, hearing, and vision disturbances. A comprehensive genetic analysis identified an unreported splice site mutation in exon 3 of the ABCD1 gene, leading to the manifestation of AMN. The inheritance pattern was consistent with X-linked recessive transmission. The article also outlines the clinical features, magnetic resonance imaging (MRI), and nerve conduction study (NCS) findings. Moreover, it discusses the genetic profile of the affected individuals and female carriers within the family. The younger sibling underwent HSCT, which was complicated by mediastinal lymph node and lung tuberculosis, adding to the complexity of managing adult ALD patients.
CONCLUSIONS: This report emphasizes the importance of genetic testing in diagnosing and comprehending the underlying mechanisms of rare genetic disorders, such as AMN with cerebral involvement. The identification of a novel splice site mutation expands our understanding of the genetic landscape of this condition. Additionally, the challenges and complications encountered during the hematopoietic stem cell transplant procedure underscore the need for cautious consideration and personalized approaches in adult ALD patients.

The development of tyrosine kinase inhibitors (TKIs) has significantly improved survival rates among patients with Philadelphia chromosome (Ph+) B cell acute lymphoblastic leukemia (B-ALL). Ph-like B-ALL patients lack the BCR::ABL1 translocation but share gene expression profiles with Ph+ B-ALL. The role of TKIs for Ph-like patients pre- and post-hematopoietic stem cell transplantation (HSCT) is not yet clear.
Here we present five cases of pediatric, adolescent, and young adult patients who presented with Ph-like B-ALL or CML in B-ALL blast phase who were treated with personalized TKI regimens pre- and post-HSCT.
This report describes several novel Ph-like fusions as well as combinations of TKIs with chemotherapy or immunotherapy not yet reported in the pediatric population. This case series provides real-world experience highlighting the potential application of pre- and post-HSCT use of TKIs in a subset of patients with targetable fusions.