Outcome of treosulfan-based reduced-toxicity conditioning regimens for HSCT in high-risk patients with primary immune deficiencies

Introduction: HSCT is the curative therapeutic option in PIDs. Due to the increase in survival rates, reduced-toxicity conditioning regimens with treosulfan have become another alternative. The purpose of this retrospective study was to analyze the outcome of treosulfan-based conditioning before HSCT for patients with PID. Method: A total of 15 patients that received a treosulfan-based conditioning regimen for HSCT were recruited. Type of diagnosis, donor and stem cell source, pretransplant organ damage, infections, engraftment, chimerism, and transplant-related toxicities were analyzed. Results: At a median follow-up time of 32 months, the overall survival was 86.7%. Following HSCT, 14 of 15 patients had engraftment, with 86.7% of the cohort having full-donor chimerism. The most common toxicity was seen on the skin (53.3%). Acute GVHD and chronic GVHD were documented in 53% and 20% of the study population, respectively. Although the cohort consisted of patients with pretransplant liver damage, SOS manifestations were documented in 20%. Conclusion: Treosulfan-based conditioning regimens before HSCT are associated with lower toxicity compared to myeloablative regimens, are safe, and have high engraftment rates with full-donor chimerism in patients having PID, regardless of the specified genetic diagnosis and donor type

Case Report: Two Patients with Partial DiGeorge Syndrome Presenting with Attention Disorder and Learning Difficulties

DiGeorge syndrome (DGS) has classically been characterized by the triad of clinical features including congenital cardiac defects, immune deficiencies secondary to aplasia or hypoplasia of the thymus, and hypocalcaemia due to small or absent parathyroid glands. The phenotypic features of these patients are much more variable and extensive than previously ecognized. The acknowledgement of similarities and phenotypic overlap of DGS with other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of DGS including palatal/speech abnormalities, as well as cognitive, neurological and psychiatric disorders. Here, we report the cases of two DGS patients with dysmorphic facial features who were initially admitted to the Psychiatry Department for attention disorder and learning difficulties

Immunoglobulin Isotype Deficiency Together with Allergic Diseases*

Giriş: Sık enfeksiyon, süt çocukluğu ve okul öncesi dönemde polikliniklere başvuru nedenleri arasında ilk sıralarda yer almaktadır. Çalışmamızda, sık enfeksiyon yakınması ile başvuran ve immünglobulin izotip eksikliği saptanan hastalarda allerjik hastalık sıklığının araştırılması amaçlanmıştır. Gereç ve Yöntem: Ankara Üniversitesi Tıp Fakültesi Çocuk İmmünoloji - Allerji polikliniğine Ocak 2013 - Şubat 2016 tarihleri arasında sık enfeksiyon yakınması ile başvuran 2592 hastanın dosya kayıtları geriye dönük olarak incelendi. Bulgular: Hastalarımızın 258'inde (%9.9) immünglobulin izotip eksikliği saptandı. Yaşları 6 ile 204 ay arasında değişen hastaların 151'i (%58.5) erkek, 107'si (%41.5) kız idi. %17'sinde eş akrabalığı öyküsü vardı. Hastaların 12'sinde (%4.6) selektif IgA eksikliği, 31'inde (%12) parsiyel IgA eksikliği, 53'ünde (%20.5) izole IgM eksikliği, 117'sinde (%45.3) süt çocuğunun geçici hipogamaglobulinemisi saptandı. 33'ü (%12.7) uzamış hipogamaglobulinemi ve 12'si (%4.6) tanımlanamayan hipogamaglobulinemi olarak değerlendirildi. 173 hastanın (%67) immünglobulin izotip eksikliği yanısıra allerjik bir hastalık tanısı da aldığı saptandı. Bu tanıların 90'ı astım, 66'sı atopik dermatit, 47'si allerjik rinokonjonktivit ve 44'ü geçici infantil vizing idi. İmmünglobulin izotip eksiklikleri arasında allerjik bir hastalık eşlik etme olasılığı açısından istatistiksel olarak anlamlı fark saptanmadı (p=0.83). Sonuç: Hastalarımızda immünoglobulin izotip eksikliğinin tipinden bağımsız olarak allerjik bir hastalık eşlik etme oranı yüksek bulunmuştur. Sık enfeksiyon yakınması ile başvuran hastalarda immün yetmezlik açısından değerlendirme yapılırken allerji semptomları da sorgulanmalıdır.Objective: Frequent infection is the most common reason for presentation to outpatient clinics during infancy and in the pre-school period. The aim of this study was to evaluate the incidence of allergic disorders in patients who apply to our allergy-immunology clinic for frequent infections and receive a diagnosis of immunoglobulin isotype deficiency.Materials and Methods: The medical records of 2592 patients who presented to the Department of Pediatric Immunology-Allergy of the Ankara University School of Medicine between January 2013 and February 2016 complaining of frequent infections were investigated retrospectively. Results: 258 (9.9%) patients had immunoglobulin isotype deficiency. The age range was 6-204 months. 151 (58.5%) were male and 107 (41.5%) were female. 17% had parental consanguinity. The diagnosis was selective IgA deficiency in 12 (4.6%), partial IgA deficiency in 31 (12%), isolated IgM deficiency in 53 (20.5%), and transient hypogammaglobulinemia of infancy in 117 (45.3%). 33 (12.7%) were considered as prolonged hypogammaglobulinemia and 12 (4.6%) as unclassified hypogammaglobulinemia. 173 (67%) patients had an allergic disease besides immunoglobulin isotype deficiency. The allergic diagnoses of the patients were asthma in 90, atopic GiRiş hastalık eşlik etme olasılığı açısından istatistiksel olarak anlamlı fark saptanmadı (p=0.83).Sonuç: Hastalarımızda immünoglobulin izotip eksikliğinin tipinden bağımsız olarak allerjik bir hastalık eşlik etme oranı yüksek bulunmuştur. Sık enfeksiyon yakınması ile başvuran hastalarda immün yetmezlik açısından değerlendirme yapılırken allerji semptomları da sorgulanmalıdır. dermatitis in 66, allergic rhinoconjunctivitis in 47 and transient wheezing of infancy in 44. There was no statistical difference between the isotypes regarding co-incidence of allergic disease and immunoglobulin deficiency (p=0.83).Conclusion: Rates of concurrence with an allergic disease regardless of the type of immunoglobulin isotype deficiency was high in our patients. One must consider that immunodeficiency may be combined with recurrent infection and atopy in patients presenting with allergy symptoms and it is important to investigate accordingly for the appropriate management of treatment

Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation

status: publishe

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Background Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.Peer reviewe