Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score
Authors: Victoria Katharina Tesch, Hassan Abolhassani, Bella Shadur, Joachim Zobel, Yuliya Mareika, Svetlana Sharapova, Elif Karakoc-Aydiner, Jacques G. Rivière, Marina Garcia-Prat, Nicolette Moes, Filomeen Haerynck, Luis I. Gonzales-Granado, Juan Luis Santos Pérez, Anna Mukhina, Anna Shcherbina, Asghar Aghamohammadi, Lennart Hammarström, Figen Dogu, Sule Haskologlu, Aydan İ. İkincioğulları, Sevgi Köstel Bal, Safa Baris, Sara Sebnem Kilic, Neslihan Edeer Karaca, Necil Kutukculer, Hermann Girschick, Antonios Kolios, Sevgi Keles, Vedat Uygun, Polina Stepensky, Austen Worth, Joris M. van Montfrans, Anke M.J. Peters, Isabelle Meyts, Mehdi Adeli, Antonio Marzollo, Nurcicek Padem, Amer M. Khojah, Zahra Chavoshzadeh, Magdalena Avbelj Stefanija, Shahrzad Bakhtiar, Benoit Florkin, Marie Meeths, Laura Gamez, Bodo Grimbacher, Mikko R.J. Seppänen, Arjan Lankester, Andrew R. Gennery, Markus G. Seidel
Journal: Journal of Allergy and Clinical Immunology (2019)

BackgroundRecent 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.ObjectiveThis international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.MethodWe 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.ResultsOf 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.ConclusionThe lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT. 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. 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. 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. 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. The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.