Prophylactic Intravenous Immunoglobulin Research Articles

Evaluation of infants administered prophylactic intravenous immunoglobulin following exposure to measles.

Intravenous immunoglobulin (IVIG) is an alternative for post-exposure prophylaxis if a vaccine is contraindicated and intramuscular immunoglobulin is unavailable. We retrospectively examined the effect of IVIG administration time on measles development in measles-contact infants younger than 6 months of age. Contact tracing of measles cases was performed by the Istanbul Public Health Directorate (IPHD) between August 24, 2012, and June 16, 2013. The mothers of 187 infants younger than 6 months were found to have negative IgG for measles. Under IPHD supervision, IVIG (0.4 g/kg) was administered to these infants within the first 6-10 days following exposure. These infants were monitored for rash and fever by IPHD for up to 28 days after IVIG prophylaxis. The study was conducted retrospectively, infants were divided into two groups, those who received IVIG at 6 days and later. These groups were compared according to the development of measles. Only 2 out of 187 infants developed measles after IVIG prophylaxis. No significant difference in measles frequency was observed between infants who received IVIG within the first 6 days after exposure and those who received IVIG after 6 days. Nine infants received IVIG in the first 3 days, and none of them developed measles. The risk of developing measles was higher in infants who had experienced contact at home (p = 0.002). IVIG administration may provide stronger protection in the first 3 days and may be given until 10 days after exposure.

Prophylactic intravenous immunoglobulin use in allogeneic stem cell transplantation; does intravenous immunoglobulin affect survival, sepsis, and engraftment time?

Abstract: BACKGROUND: Stem cell transplant recipients have an increase in various infections depending on the immunosuppression. The purpose is to explore the effect of the use of proflactıc intravenous immunoglobulin (IVIG) on transplant recıpıents. OBJECTIVE: It was aimed to examine the effect of IVIG on allogeneic stem cell transplantation. MATERIALS AND METHODS: In this study, sepsis status, infection focus causing sepsis, neutrophil and platelet engraftment time of patients the length of stay in the hospital at the time of the stem cell transplant, if the patient died, how many days after the transplant the event developed, and the data of the bone marrow transplant unit were reviewed retrospectively. One hundred and eleven patients who were given IVIG (400 mg/kg/week IVIG intravenous was given to the patients as a weekly prophylactic up to 100 days starting on the 7th day after transplantation) and 190 patients who did not receive IVIG were included in the study. RESULTS: There was no statistically significant difference between the IVIG groups in terms of gender, diagnosis, donor characteristics, and event (P > 0.05). Sepsis was observed significantly less in patients who were given IVIG compared to patients who were not given IVIG (P < 0.001). While it was observed that IVIG did not have a significant effect on platelet engraftment and discharge times (P > 0.05), neutrophil engraftment time was significantly higher in patients given IVIG compared to patients not given IVIG (P < 0.009). It was observed that the use of IVIG in patients with sepsis did not have a positive effect on survival. (with sepsis hazard ratio [HR]: 3.890 P = 0.001, IVIG given HR: 3.244 P = 0.035). CONCLUSION: It was observed that the use of IVIG in allogeneic stem cell transplantation was associated with a decrease in sepsis, but the use of IVIG did not have a positive effect on survival and could prolong neutrophil engraftment.

Drug-induced Liver Injury from Intravenous Immunoglobulin for Prevention of Recurrent Gestational Alloimmune Liver Disease: A Clinical Catch-22

Gestational alloimmune liver disease (GALD) is a rare autoimmune syndrome in which maternal antibodies lead to in utero fetal hepatocyte destruction, often presenting as neonatal liver failure and hemochromatosis. Antenatal intravenous immunoglobulin (IVIG) is generally accepted to be safe in pregnancy with demonstrable benefits for reducing GALD recurrence risk in subsequent pregnancies. Here we present a case of a 33-year-old woman with a prior neonatal demise due to GALD who received multiple prophylactic IVIG infusions in a subsequent twin pregnancy complicated by maternal jaundice and acute hepatitis. A liver biopsy demonstrated hepatocellular injury with bridging necrosis and cholestatic features consistent with drug-induced liver injury. This case demonstrates the importance of close clinical monitoring during IVIG therapy and the need for further research into alternative prophylaxis options for GALD. Key Points

Flat dose intravenous immunoglobulin (IVIG) for primary infection prophylaxis after CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).

e19004 Background: Prolonged hypogammaglobulinemia is a common side effect of CD19 chimeric antigen receptor (CAR) T-cell therapy for B-NHL. Average infection rates 1 year (yr) post CAR-T are 44-53% (Kampouri, Tran Infect Dis 2023). Prophylactic IVIG is typically dosed by weight; however, optimal dosing strategy remains unknown. We explored the efficacy of reduced flat IVIG dose on infection rates and non-relapse mortality (NRM) post CAR-T. Methods: B-NHL pts who received commercial CD19 CAR-T therapy from Nov 2017 to Mar 2023 at Vanderbilt Medical Center were included. All pts were on trimethoprim-sulfamethoxazole and valacyclovir for prophylaxis. IVIG at a flat dose of 10 grams was given for IgG < 400 mg/dL. Relevant clinical variables were collected from day 30 to 1 yr. Infections were defined as mild (treated outpatient), moderate (required admission), or severe (required intensive care unit) and by CTCAE v5 criteria. Severe neutropenia was defined as ANC<500 and severe lymphopenia was ALC<500. NRM was defined by death without progression or relapse. Estimated cost of therapy was $140/gram of IVIG based on previously published data. Results: A total of 43 pts (35 large cell lymphoma, 7 mantle cell lymphoma, and 1 follicular lymphoma) with median follow up of 445 days (range 134-2141) were included. Axicabtagene ciloleucel was given to 34 pts (79%), tisagenlecleucel to 2 pts (5%), and brexucabtagene autoleucel to 7 pts (16%). Median age was 58 (range 22-81). Median number of pre CAR-T therapies was 3 (range 1-7). There were 52 total infections with median time to first infection of 165 days (range 31-365). Of all infections, 21 (40%) were viral, 29 (56%) bacterial, and 2 (4%) fungal. There were 31 (60%) mild infections, 19 (36%) moderate, and 2 (4%) severe. Multiple G≥3 infections occurred in 14 pts (33%). At first infection, 4 pts (10%) had severeneutropenia and 13 pts (31%) had severelymphopenia. IVIG was given to 27 pts (63%). Median IgG at D30 was 438 mg/dL (range 143–1099) and 414 mg/dL (range 133–842) at D60. Prolonged IgG≤400 at 6 months occurred in 15 pts (35%). Median IVIG cost using flat dosing was $2800 (range $0-12,600) compared to a median cost of $8,075 (range $0-76,642) if weight-based dosing was utilized. NRM was 9% (4 pts). Of those pts, only 1 had a G≥3 infection during the first-year post CAR-T. Conclusions: We demonstrate comparable infection rates 1 yr post CD19 CAR-T and low NRM with the use of 10g flat IVIG dosing for consecutively treated pts. In addition, only 1 of 4 pts with NRM had severe infection within 1 yr. Notably, 35% of pts had persistent hypogammaglobulinemia at 6 mo and use of a flat dosing schedule provided substantial cost reduction. These findings should be validated in a prospective randomized trial.

Clinical efficacy of prophylactic intravenous immunoglobulin for elderly DLBCL patients with hypogammaglobulinemia in the COVID-19 pandemic era.

Elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population. A total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes. Among the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis. IVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG's potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P=.002) compared with the control group. Additionally, the time duration of CMV reactivation (P=.001) and bacterial infection rate (P=.013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P=.006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

Hypogammaglobulinemia and Infection Risk in Relapsed Refractory B Cell Malignancy Patients Treated with Varnimcabtagene Autoleucel (IMN-003A), a CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in the Phase-2 Study (IMAGINE)

Background: Varnimcabtagene autoleucel (IMN-003A) is an anti-CD19 CAR-T cell immunotherapy for patients with relapsed refractory B cell malignancies (RR BCM) in the Phase 2 IMAGINE study. Hypogammaglobinemia can result from normal CD19+ B cell depletion (on-target, off-site effect) by CD19 directed CAR-T cells. RR BCM patients (pts) are already at risk for infections due to impaired immune function, lymphodepletion preparative regimen and prior immunosuppressive therapies. Intravenous immunoglobulin (IVIg) replacement is used to reduce the risk of infections due to hypogammaglobulinemia. We report the impact of var-cel on hypogammaglobinemia, infectious complications, risk factors, IVIg usage and clinical outcomes for RR BCM patients treated in first-in-India industry study (CTRI/2022/03/041162). Methods: RR BCM pts treated with var-cel in this study were reviewed. Hypogammaglobulinemia was defined as IgG <4 g/L. Infections reported during pre-apheresis (post screening), D0 to D+28 post CAR-T infusion and beyond D+29 for study duration were analyzed. IVIg usage for hypogammaglobulinemia was at investigator discretion. Patients were monitored for infection events. RR BCM response was assessed as per NCCN (B-ALL) and IWG (B-NHL) criteria. Appropriate statistical tools were used for data analysis. Results: At data cut-off, of 25 pts enrolled (median age 31 yrs, range 3 - 66) with RR BCM (n=13 B-ALL; n=12 B-NHL), 24 pts received var-cel (1 withdrawal). Median follow-up after IMN-003A administration was 205 days (range 12 - 434). Overall response rate (ORR) was 91.7% (22/24) at D+28 (B-ALL 91.7%; B-NHL 91.7%) and 80.9% (17/21) at D+90 (B-ALL 80%; B-NHL 81.8%). Treatment related mortality was 4.2% (n=1/24); 3 pts died of disease progression. Of the 24 pts, none had hypogammaglobulinemia (IgG <4g/L) at baseline. Eleven pts (45.8%) developed hypogammaglobulinemia post var-cel infusion. Of these, 10 pts (90.9%) received prophylactic intravenous immunoglobulin (IVIg). In total, 70.8% (n=17/24) pts received IVIg infusions (Table 1). The median time to initiation of IVIg after var-cel infusion was 58 days (range 15 to 189 days). Of evaluable pts, IVIg was used in 15 of 17 (88.2%) responders at D+90 (CR / PR) vs 0 of 4 (0%) in non-responders (SD / PD) (p=0.06). 52.9% (n=9/17) pts on prophylactic IVIg reported infections. Patients who received IVIg had more infections (30 events; p=0.76). The mean number of infections with and without IVIg was 1.8 and 1.6 respectively. The median overall survival was significantly higher in pts who received IVIg prophylaxis (p=0.02). There was no difference in survival observed based on presence or absence of hypogammaglobulinemia post var-cel infusion (p=0.46). A total of 41 infections were reported in 13 pts. Of these, the incidence from screening to D-1; D0 to D+28 and beyond D+29 were 9 events (4 pts); 12 (11) and 20 (7) respectively. Bacterial, viral and fungal infections reported were 28 events (11 pts); 12 (8) and 1 (1) respectively. Bacterial infections were sepsis (n=7); urinary tract infections (n=5), respiratory (n=14) and central line (n=2). There were 12 viral events, 11 of respiratory origin and one involving conjunctiva. There was one episode of probable fungal candidemia. Stool surveillance detected 27 positive events in 13 pts. Table 2 summarizes the reported infectious organisms. There were 23 infections documented in 13 patients who did not develop hypogammaglobulinemia (median 2 infections; mean 1.8; range 1 - 6). Of 11 pts with hypogammaglobulinemia, there were 18 infections (median 3.5; mean 1.6; range 1 - 9). Complete and partial responders had more infections compared to non-responders (p = 0.05). Conclusions: This is the first-in-India report evaluating hypogammaglobulinemia and infection risk post CAR-T cell infusion. The IVIg usage and documented infections was more in responders. The safety and efficacy outcomes of varnimcabtagene autoleucel (IMN-003A) are consistent with reported outcomes of approved CD19 directed CAR-T cell therapies. The use of prophylactic IVIg, often led by individual practice, to reduce the number of infections and its impact on efficacy outcomes remains uncertain. Potential strategies to reduce infection risk may help improve outcomes.

Immune Reconstitution and Infection Patterns Following CAR T-Cell Therapy in Patients with Aggressive Lymphoma

Introduction: Chimeric antigen receptor T-cell therapy (CAR T) is an effective therapy in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) but is associated with prolonged cytopenias, persistently low CD4 T-cells, and hypogammaglobulinemia (defined as serum IgG <500 mg/dL) resulting in an immunocompromised state post CAR T [Logue 2021]. Prophylactic antimicrobials and intravenous immunoglobulin (IVIG) have been utilized to mitigate infectious complications, but practices are not standardized. We sought to examine patterns of immune reconstitution and their impact on incidence, timing, and management of infection following CAR T. Methods: We identified patients (pts) with R/R LBCL treated with CAR T between 2015 - 2022 across 13 academic institutions. Data on measures of immune recovery and infections were captured post CAR T. Time-to-event curves were established by Kaplan-Meier method. Results: 582 pts were included with a median age of 62 yrs (range 19-89). Pts were heavily pretreated with 3 median lines (range 1-18), and 26% with prior autologous transplant. Median time to ANC > 500 cells/mm3 was 11 days (D); median CD4 counts were 155 and 223 cells/mm 3 at 6 and 12 mo, respectively. Median absolute neutrophil and lymphocyte counts at 6 mo were 2300 and 690 cells/mm 3, respectively. At D90 post-CAR T, 61.5% (136/221) of pts had hypogammaglobulinemia (HGG) that persisted in 62.1% (90/145) at 1yr and 48.3% (56/116) at 2yrs. Data for D90-2 yrs post CAR T were analyzed to characterize late effects of CAR T as follows: Figure 1 describes time to first infection by organism of interest. 66.8% (193/389) of pts developed bacterial infections; median time to infection was 6.7 mo. Most common organisms were Pseudomonas (n =33), E. Coli (n=24), S. Aureus (n=22), C. Diff (n=26), Klebsiella (n= 18). HGG at D30 and D90 was associated with increased risk of bacterial infection, p = 0.002 (OR 2.5) and p= 0.013 (OR 2.1), respectively. Low CD4 counts and neutropenia at any time point within 2 years, did not correlate with increased rate of bacterial infection. Excluding COVID, 31.2% (138/443) of pts developed viral infections; median time to infection was 5.4 mo. Most common organisms were COVID (n=49), Rhinovirus (n= 20), CMV (n= 21), and Influenza (n= 13). Median time to COVID infection was 15.6 mo (range 0.2- 33.1). Neither neutropenia, nor low CD4 counts within 2 yrs post CAR T correlated with increased rate of viral infection. HGG at any time point within 6 mo post CAR T was associated with increased risk of viral infections, including COVID (p = 0.04, OR 2.2). Fungal and PJP infections were infrequent, occurring in 19 and 6 pts, respectively. Median time to fungal infection was 1.7 mo. For infection risk mitigation: 98.4% (496/504) of pts received prophylactic antivirals for median duration of 9.0 mo (0.2- 80.0) and 74.5% (371/498) received PJP prophylaxis for median duration of 6.3 mo (0.2-62.6). IVIG was administered in 34.3% (192/560) of pts with median time to initiation of 3.9 mo post CAR T. Pts with infection D90- 2 yrs were more likely to receive IVIG than those without infection (43.5% vs 26.9% respectively, p= 0.001). Median follow-up in living pts was 35.3 mo with median OS of 27.8 mo (CI 21.2-34.5). Ninety-six (16.5%) pts received salvage therapy post CAR T. Infection of all types <90 days post- CAR T was associated with inferior OS (16 mo vs 43.3 mo, p=0.001). Infection >90 days-2 yrs post CAR T was not associated with worse OS. Presence of HGG at any time point did not impact OS (p = 0.218). However, median OS was not reached in pts who received IVIG vs 16.9 mo in pts who did not (Figure 2, p= 0.001). Furthermore, in pts with HGG, lack of IVIG utilization at D90 was associated with worse OS (p <0.001). Conclusions: Immune suppression is a long-term toxicity of CAR T. Bacterial infections were common and most occurred within ~ 7 mo of infusion while viral infections were less frequent and occurred earlier. Both were associated with prolonged HGG. These observations should inform use of early antimicrobial prophylaxis. The majority of pts received anti-viral and PJP prophylaxis which may have contributed to lower rates of these infections. Pts with infection were more likely to receive IVIG with administration of IVIG improving survival. Our results support continued use of antiviral and PJP prophylaxis and the consideration of empiric IVIG within 30 days following CAR T to mitigate risk of infection and improve survival following CAR T.

Ocular toxoplasmosis during frontline venetoclax therapy for chronic lymphocytic leukaemia - more than meets the eye.

A 67-year-old woman presented with a right central scotoma and reduced Snellen visual acuity (<6/60), 4 months after commencing frontline obinutuzumab–venetoclax (Ven–O) therapy for 13q-deleted, IGHV-mutated, chronic lymphocytic leukaemia (CLL). At the time of ocular symptoms, her full blood count comprised haemoglobin 131 g/L, lymphocytes 0.7 × 109/L, neutrophils 0.8 × 109/L, platelets 40 × 109/L and total IgG < 3.2 g/L. Repeat bone marrow trephine revealed minor residual CLL only (5%–10%). She received valaciclovir only as supportive therapy. Serial ophthalmic examinations demonstrated an enlarging macular lesion with mild vitritis consistent with retinochoroiditis (retinal photograph, Figure 2 without satellite lesions or evidence of pre-existing retinal scarring. Spectral-domain optical coherence tomography Figure 1 revealed full-thickness retinal necrosis with hyper-reflectivity and disorganisation of retinal layers. Polymerase chain reaction (PCR) of aqueous humour demonstrated the presence of Toxoplasma gondii, consistent with active ocular toxoplasmosis. T. gondii IgG but no IgM antibodies were detected both pre-treatment and 4 weeks from the onset of ocular symptoms. Computed tomography imaging of the brain was normal, and serum T. gondii PCR was negative. T. gondii is a common infectious cause of retinochoroiditis. Both acquired ocular toxoplasmosis and reactivation of previous infection may be observed in immune-competent individuals. Ocular toxoplasmosis has also been described in relapsed/refractory CLL, including those treated with continuous venetoclax. Prior fludarabine exposure has been cited as a risk factor for opportunistic infection. However, reports of toxoplasmosis during frontline CLL therapy are limited and, to our knowledge, have not included the Ven–O combination. The patient completed systemic and intra-vitreal clindamycin with topical prednisolone drops, noting gradual improvement of her visual acuity to 6/36 and slow healing of the macular lesion on serial examination. Given the quantitative immune dysfunction observed and evidence of past T. gondii infection, opportunistic reactivation of toxoplasmosis was considered. However, the absence of pre-existing toxoplasmosis retinal scar or bilateral ocular involvement argued against infection reactivation. Absence of infection dissemination, including no central nervous system involvement as seen with acquired immune deficiency syndromes such as HIV, also argue against infection occurring as a function of immune compromise. Nonetheless, our patient remains on suppressive antibiotic therapy during Ven–O therapy and 4-weekly prophylactic intravenous immunoglobulin. This case highlights the complexities of infection diagnoses and management in the context of frontline novel therapies in CLL. Appropriate supportive treatments remain uncertain. Rory Bennett, Lyndell L. Lim, Constantine S. Tam interpreted the case information and wrote the manuscript. CST: Honoraria for AbbVie, AstraZeneca, Janssen, BeiGene and LOXO. Research funding from AbbVie, Janssen and BeiGene Documented verbal consent obtained from the patient prior to preparation of manuscript.

Predicting Risk of Infection Based on Immunoglobulin Nadirs after CD38 Monoclonal Antibody Treatment in Multiple Myeloma

Background: Anti-CD38 monoclonal antibodies are used to treat newly diagnosed and relapsed or refractory multiple myeloma. Previous studies have shown an increased risk of infection while on daratumumab due to the immunosuppressive effect on malignant and normal plasma cells. We sought to retrospectively analyze and further understand the correlation of immunoglobin levels and risk of infection during treatment with anti-CD38 monoclonal antibodies in Multiple Myeloma. Methods: Analysis was performed on data from 261 patients who had received anti-CD38 monoclonal antibody therapy as part of treatment for multiple myeloma between November 11, 2016, and May 11, 2022. 51.7% were male and 48.3% were female. 47.1% of the patients identified as Black, 46% as White, and 6.9% as other races. 14.9% of the patients had Stage I, 41.8% had Stage II and 17.2% had Stage III disease, based on the Revised International Staging System (RISS). Baseline renal disease was present in 35.6% of patients. Median number of anti-CD38 Monoclonal antibody infusions was 16. We examined rates of specific infections (determined by ICD-10 codes), including pneumonia, urinary tract infection, bacteremia, and sepsis, as well as emergency room visits, hospitalizations including ICU stays for up to a year after completing treatment. These rates were correlated with immunoglobulin levels, absolute lymphocyte count, and the presence of concomitant treatment with a proteasome inhibitor or immunomodulator. Results: The overall infection rate among patients receiving anti-CD 38 monoclonal antibody treatment was 32.6%. Bacterial infection developed in 22.2%, viral infections in 17.6%, and fungal infections in 3.4% of patients. SARS-CoV-2 infection rate was 13.4%. The median number of infusions was 15 in those without an infection and 20 in those who developed an infection (p<0.001).19.2% of patients who began anti-CD38 monoclonal antibody treatment during the study period have expired, of whom 56.0 % had an infection. Higher rates of infection were noted with lower IgA levels (p=0.007). There was no significant difference in infection rate with lower IgG and IgA levels or lower absolute lymphocyte levels (p=0.054). However, in patients with an infection there was a longer duration of sub-normal IgG days (114 vs 287 days, p=<0.001), IgA (119.5 vs 215, p=0.006), and IgM (161 vs 274.5, p=0.011). 44.4% of patients had an emergency room visit of whom 40.0% were due to infections (p=0.113). 66.9% of patents required hospital admissions of whom 43.2% had an infection) p<0.001). 18.5% of treated patients required ICU stays of whom 63.9% had an infection) p<0.001). Discussion:Conclusions: A longer duration of subnormal Immunoglobulin levels correlated with higher risk of infection in Multiple Myeloma patients treated with anti-CD 38 monoclonal antibodies. Lowest Ig A levels during treatment correlated with a higher rate of infection while lowest IgG levels did not. Patients who developed infectious complications while on treatment with anti-CD 38 monoclonal antibodies had a significantly higher risk of hospitalization, ICU stays, and death. Prophylactic intravenous immunoglobulin can be studied to evaluate mitigation of infection in the highest risk subpopulation identified in this analysis such as those with prolonged subnormal Immunoglobulin levels. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Vaccine Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy

Background: While CD19 chimeric antigen receptor T cell therapy (CAR-T) therapy does not use myeloablative chemotherapy, patients with aggressive lymphoma treated with CAR-T are immunosuppressed from lymphodepletion chemotherapy, and prolonged B cell aplasia and hypogammaglobulinemia from CAR-T. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) has not been formally studied. We report the vaccine titers of patients treated with CAR-T at Mayo Clinic, Rochester.Methods: We conducted a retrospective chart review of patients who received CAR-T from 9/2018 to 4/2021 for treatment of aggressive lymphoma at Mayo Clinic, Rochester. Data was collected on anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 post CAR-T. Clinical assays for vaccine titers were used for patient assessment and threshold for clinical assays was used to define antibody titer as positive or negative.Results: In our cohort of 87 CAR-T patients, 83 (94%) patients were infused with axicabtagene ciloleucel, 4 (5%) patients received brexucabtagene autoleucel and 1 (1%) received tisagenlecleucel. Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Streptococcus pneumoniae (Strep PNA). Similar trends were seen whether patients had autologous stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table 1).At 3 months post CAR-T, overall seropositivity rates were similar when compared to pre-CAR-T levels for the prior transplant and no prior transplant group. For patients who had received intravenous immunoglobulin (IVIG) supplement prophylactically (for IVIG<400 mg/dl), seropositivity rate for Strep PNA remained zero (Table 1). Among the 30 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (3/5, 60%), rubella (3/4, 75%), varicella-zoster (VZV, 4/4, 100%), hepatitis A (8/9, 89%) and hepatitis B (10/12, 83%).For patients who did not receive IVIG prophylaxis after CAR-T, seropositivity rate for hepatitis A and B was low. In addition, some of these patients had a loss of seropositivity for Strep PNA (2/5, 40%) and hepatitis A (1/4, 25%).Conclusion: The presence of protective vaccine titers is variable for patients receiving CAR-T therapy, regardless of recent ASCT. The loss of protective titers post CAR-T was low. The need for immunization post CAR-T may remain important regardless of transplant status prior to CAR-T. Prophylactic IVIG does not confer complete immunization protection. Optimal timing for immunization post CAR-T is probably unknown and may need to be considered earlier for patients not on prophylactic IVIG. Further study with longer follow-up is needed to inform the need for immunization and optimal timing post CAR-T. [Display omitted] DisclosuresBennani: Kymera: Other: Advisory Board; Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board. Paludo: Karyopharm: Research Funding. Wang: LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; InnoCare: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Sorrento: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Juno: Consultancy; Legend: Consultancy; Gamida Cell: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India.

BackgroundWiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India.MethodsRequest to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed.ResultsIn this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months).ConclusionsWe report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.

Early Experience of ABO-incompatible Living Donor Liver Transplantation in Haeundae Paik Hospital

Introduction: ABO-incompatible LDLT (ABOi-LDLT) could be a useful option for expanding pool of available organs. Since the introduction of rituximab in ABOi-LDLT, the incidence of AMR dropped dramatically and the paradigm of ABOi-LDLT in adult patients has changed. Methods: We would like to present our initial experience of three cases of ABOi-LDLT. The protocol includes a single dose of rituximab (300 mg/m2) 3 weeks before transplantation, several sessions of plasmapheresis to decrease the isoagglutinin (IA) titer to ≤ 1:32, and a triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil, and steroid. Results: All three patients performed a relatively large number of plasmapheresis to reach the target IA titers (16, 19, and 7 sessions, respectively). The IA titers immediately before transplantation were 32, 1024 and 128, respectively, while the peak titers during post-transplant period were 32, 128, and 32, respectively. In particular, case 2 patient has severe rebound elevation of IA titer even after administration of Bortezomib, a proteasome inhibitor that depletes plasma cells. As for this patient, we should perform LDLT at an IA titer 1:1024 with splenectomy and prophylactic intravenous immunoglobulin. Two patients (case 1, 2) are alive with no evidence of AMR until now, but one patient (case 3) died at POD51 due to hepatic artery thrombosis and sepsis. Conclusions: Rituximab-based protocol is a cornerstone in the regimens of desensitization for ABOi-LDLT, but more study on pre-transplant target IA titer and effectiveness of pre-transplant plasmapheresis needs to be continued as seen in the present cases.

Steroid Use, Advanced Stage Disease and ≥3 Lines of Prior Chemotherapy Are Associated with a Higher Risk of Infection Following CD19 CAR T-Cell Therapy for B-NHL: Real World Data from a Large UK Center

Steroid Use, Advanced Stage Disease and ≥3 Lines of Prior Chemotherapy Are Associated with a Higher Risk of Infection Following CD19 CAR T-Cell Therapy for B-NHL: Real World Data from a Large UK Center

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants.

Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in immunoglobulin G (IgG); therefore, administration of intravenous immunoglobulin (IVIG) may have the potential of preventing or altering the course of nosocomial infections. To use systematic review/meta-analytical techniques to determine whether IVIG administration (compared with placebo or no intervention) to preterm (< 37 weeks' postmenstrual age (PMA) at birth) or LBW (< 2500 g birth weight) infants or both is effective/safe in preventing nosocomial infection. For this update, MEDLINE, EMBASE, CINAHL, The Cochrane Library, Controlled Trials, ClinicalTrials.gov and PAS Abstracts2view were searched in May 2013. We selected randomised controlled trials (RCTs) in which a group of participants to whom IVIG was given was compared with a control group that received a placebo or no intervention for preterm (< 37 weeks' gestational age) and/or LBW (< 2500 g) infants. Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded, as were studies in which the follow-up period was one week or less. Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group. Nineteen studies enrolling approximately 5000 preterm and/or LBW infants met inclusion criteria. No new trials were identified in May 2013. When all studies were combined, a significant reduction in sepsis was noted (typical risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74 to 0.98; typical risk difference (RD) -0.03, 95% CI 0.00 to -0.05; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 20 to infinity), and moderate between-study heterogeneity was reported (I2 54% for RR, 55% for RD). A significant reduction of one or more episodes was found for any serious infection when all studies were combined (typical RR 0.82, 95% CI 0.74 to 0.92; typical RD -0.04, 95% CI -0.02 to -0.06; NNTB 25, 95% CI 17 to 50), and moderate between-study heterogeneity was observed (I2 50% for RR, 62% for RD). No statistically significant differences in mortality from all causes were noted (typical RR 0.89, 95% CI 0.75 to 1.05; typical RD -0.01, 95% CI -0.03 to 0.01), and no heterogeneity for RR (I2 = 21%) or low heterogeneity for RD was documented (I2 = 28%). No statistically significant difference was seen in mortality from infection; in incidence of necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) or intraventricular haemorrhage (IVH) or in length of hospital stay. No major adverse effects of IVIG were reported in any of these studies. IVIG administration results in a 3% reduction in sepsis and a 4% reduction in one or more episodes of any serious infection but is not associated with reductions in other clinically important outcomes, including mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects. The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for conducting additional RCTs to test the efficacy of previously studied IVIG preparations in reducing nosocomial infections in preterm and/or LBW infants.

Phenotypic and Transcriptomic Lymphocytes Changes in Allograft Recipients After Intravenous Immunoglobulin Therapy in Kidney Transplant Recipients.

High dose intravenous immunoglobulin (IVIG) are widely used after kidney transplantation and its biological effect on T and B cell phenotype in the context of maintenance immunosuppression was not documented yet. We designed a monocentric prospective cohort study of kidney allograft recipients with anti-HLA donor specific antibodies (DSA) without acute rejection on screening biopsies treated with prophylactic high-dose IVIG (2 g/kg) monthly for 2 months. Any previous treatment with Rituximab was an exclusion criterion. We performed an extensive analysis of phenotypic and transcriptomic T and B lymphocytes changes and serum cytokines after treatment (day 60). Twelve kidney transplant recipients who completed at least two courses of high-dose IVIG (2 g/kg) were included in a median time of 45 (12–132) months after transplant. Anti-HLA DSA characteristics were similar before and after treatment. At D60, PBMC population distribution was similar to the day before the first infusion. CD8+ CD45RA+ T cells and naïve B-cells (Bm2+) decreased (P = 0.03 and P = 0.012, respectively) whereas Bm1 (mature B-cells) increased (P = 0.004). RORγt serum mRNA transcription factor and CD3 serum mRNA increased 60 days after IVIG (P = 0.02 for both). Among the 25 cytokines tested, only IL-18 serum concentration significantly decreased at D60 (P = 0.03). In conclusion, high dose IVIG induced limited B cell and T cell phenotype modifications that could lead to anti-HLA DSA decrease. However, no clinical effect has been isolated and the real benefit of prophylactic use of IVIG after kidney transplantation merits to be questioned.

Risk of Serious Infections with Carfilzomib in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Infections are an important cause of morbidity and mortality in multiple myeloma [MM]. Infections can be a result of the underlying disease or toxicity of anti-myeloma therapy or both. Proteasome inhibitors [PI] are associated with a risk of infection due to several mechanisms including decreased cytotoxic T-cell and natural killer cell proliferation, inhibition of dendritic cell function, and suppression of polyclonal immunoglobulins. Carfilzomib is an irreversible PI, with a higher potency compared to bortezomib in preclinical studies. Although infections are frequently reported as adverse events with carfilzomib-based combination regimens, definitive data on increased infection risk with carfilzomib is lacking. Hence, we conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to estimate the relative risk of serious infections associated with the use of carfilzomib-based regimens in MM. Methods: A systematic electronic search was performed in Ovid MEDLINE, Ovid EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov with appropriate search terms through March 20, 2019. We included RCTs comparing carfilzomib-based regimens with non-carfilzomib based regimens in MM. Primary outcome of our analysis was to estimate the relative risk of serious infections with carfilzomib. Data on primary outcome was obtained from ClinicalTrials.gov records of the included studies. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of the random-effects model by Der Simonian and Laird. Heterogeneity of effect size was quantified using I2 statistic. Publication bias was assessed by the Egger's regression test. All statistical analyses were performed with Review Manager (RevMan Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration). Results: A total of 3,683 unique records were screened, among which, four RCTs including a total of 2954 patients (1486 in carfilzomib arm and 1468 in control arm) were included in the final analysis. Characteristics of studies included in the analysis are summarized in table 1. All but one study (CLARION) were conducted in relapsed/refractory MM. Carfilzomib was administered twice weekly in all trials, with dose ranging from 20/27 to 20/56 mg/m2. The median duration of treatment ranged from 16 to 88 weeks. Other than FOCUS trial which had single-agent carfilzomib, all had carfilzomib-based combination regimens in the intervention arm, namely, carfilzomib-dexamethasone, carfilzomib-lenalidomide-dexamethasone, and carfilzomib-melphalan-prednisone. The risk of total serious infections was significantly elevated with carfilzomib-based regimens compared to other agents [pooled RR 1.40, 95% CI: 1.17 - 1.69, p = 0.0003, I2 = 57%, figure 1]. In the carfilzomib arm, 65% of all serious infections involved the respiratory tract, and 38% were serious pneumonia. Patients on carfilzomib-based regimens were at a significantly higher risk of serious respiratory tract infections (RTI) in comparison with those on other treatments [pooled RR 1.30, 95% CI: 1.12 - 1.50, p = 0.0004, I2 = 0%, figure 2]. However, there was no significant difference in the incidence of serious pneumonia between carfilzomib and control groups [pooled RR 1.14, 95% CI: 0.92 - 1.41, p = 0.23, I2 = 15%, figure 3]. None to substantial levels of heterogeneity were noted across trials, depending on the type of analysis. Subgroup analysis based on carfilzomib dose (≤ 27 vs. &gt;27 mg/m2) and treatment setting (relapsed/refractory vs. newly diagnosed) did not reveal any statistically significant subgroup effect. There was no publication bias among studies. Conclusion: In our meta-analysis, carfilzomib is associated with a 40% increased relative risk of serious infections in patients with MM. The most common site of infection is the respiratory tract. Although carfilzomib leads to a higher risk of serious RTIs, the risk of serious pneumonia was not significantly different compared to controls. These findings will assist clinicians with risk-benefit assessment prior to initiation of carfilzomib-based regimens. Future studies should investigate patient-related and disease-related risk factors for serious infections and the utility of prophylactic antibiotic or intravenous immunoglobulin in high-risk patients. Disclosures No relevant conflicts of interest to declare.

Septicemia after Chemotherapy for Acute Lymphoblastic Leukemia: A Multicenter Study Chinese Children Cancer Group (CCCG)-ALL-2015

Introduction: Septicemia is one of the common complications after chemotherapy for acute lymphoblastic leukemia (ALL) and is also an important cause of treatment related mortality and treatment failure. A multicenter study CCCG-ALL-2015 was conducted in China and factors associated with septicemia and mortality were studied. Methods: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included in this study. Patients with documented septicemia were identified from the Database of Central Data Center. Additional data were then collected from participation centers, including associated co-morbidity, blood counts before septicemia and infection preventive measures. Results: A total of 4080 patients were recruited from 18 centers. There were 527 patients with septicemia identified (12.9%). The Intermediate risk (IR)/ High risk (HR) group(n=1930) had significantly higher incidence of septicemia as compared with Low risk (LR) group (n=2150), 17.15% vs 9.12% (p&lt;0.001). Among the IR/HR group, children with Philadelphia (Ph) positive ALL (n=166) had similar incidence of septicemia as compared with Ph negative group (n=1764), 20.5% vs 16.8% (p =0.14). Induction phase was the period with most septicemia episodes occurred, 66.3% in LR and 56.1% in IR/HR groups. There was another peak of septicemia in IR/HR group during the re-induction phase (18%) and early maintenance phase at week 35-54 (9.3%). Gram positive bacteria accounted for 54.2%, Gram negative bacteria 44.5% and fungus 1.4% of positive cultures. The top 10 isolates were Coagulase negative staphylococcus (20.1%), staphylococcal epidermidis (14.6%), E. Coli (11.5%, 29/68 were ESBL), klebsiella pneumonia (8%, 7/47 were ESBL), pseudomonas aeruginosa (7%, 2/41 were ESBL), staphylococcus aureus (5.6%, 8/33 were MRSA), streptococcal mitis (3.2%), streptococcal pneumonia (3%), salmonella (2%) and Enterobacter cloacae (1.7%). Multi-drug resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.2%. Multiple logistic regression identified female gender, comorbid complications and fungal infection as risk factors associated with mortality. Gram negative septicemia was also associated with higher mortality, 4.9% vs 1.9% (P&lt;0.05%). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. Centers allowed additional beds opened in the ward due to full occupancy had higher incidence of septicemia, 16.3% (342/2101) vs 11% (218/1979), p &lt;0.001. Centers with the practice of using modular High Efficiency Particulate Air (HEPA) filter units in the wards for patients with severe neutropenia had lower incidence of septicemia, 8.3% (118/1430) vs 16.7% (442/2650), p&lt;0.001. Prophylactic use of G-CSF at time of neutropenia (neutrophils &lt; 0.5x109/L) was also associated with lower incidence of septicemia, 10.1% (165/1626) vs 16.1% (442/2650). Similarly prophylactic intravenous immunoglobulin and antibiotics was also associated with lower incidence of septicemia, 8.9% (78/877) vs 15% (481/3203) and 7.8% (70/970) vs 18.7% (490/3110) respectively. Conclusion: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to reports of western countries. The septicemia related mortality rate was low. However there was marked variation in the incidence of septicemia among the centers, further studies are required to validate factors such as infection preventive measures which might influence the septicemia incidence. Disclosures No relevant conflicts of interest to declare.

PB2351 ALLOGENEIC TRANSPLANT EXPERIENCE IN ADULT PATIENTS WITH PRIMARY IMMUNODEFICIENCY

Background:Primary immunodeficiencies (PIDs) are associated with recurrent infections with multipl microbial agents. The prevelance of PID diseases are high in Turkey, where consanguineous marriages are common. In primary immunodeficiencies, allogeneic hematopoietic stem cell transplantation (allo‐HCST) is mostly performed during childhood. Due to lack of experience and previous poor results, there is debate about the optimal timing and use of allo‐HCST in adults.Aims:The aim of this presentation is to report the results of allogeneic HSCT from matched unrelated donor (MUD) in four adult patients with diagnosis of PID.Methods:The results of allo‐HCST of 4 adult patients (3 male and 1 female) with diagnosis of PID were evaluated retrospectively. Median age was 22 years. Patients had intensive history of infection such as bronchiectasis, penile HPV, tuberculosis and suppurative soft tissue infection of the head and neck. Demographic characteristics of patients, conditioning regimens, donor characteristics, stem cell source and amount, graft versus disease (GvHH) prophylaxis are given in table 1.The busulfan dose was kept in the effective range by calculating the area under the curve.They were ordered prophylactic intravenous immunoglobulin (IVIg) 0.4 g/kg weekly. Viral loads for EBV and CMV were weekly screened by PCR.Results:Median follow‐up time is 10 months (range: 5‐13 months). Neutrophil and platelet engraftment took place on median days 15 (range:11‐17 days) and 12.5 (range.8‐20), respectively. Patient no 1 lived grade 4 gastrointestinal truct GvHD, grade 2 lung GvHD and grade 2 skin GvHD. Grade 4 gastrointestinal truct and grade 3 liver GvHD were occured in patient no 2. Both of them were treated with ruxolitinib, mesenchymal stem cell and extracorporeal photopheresis according to clinical picture of the patients. The donor chimerism on day 90 was found to be median 99% (range:98% &gt; 100%) for three patients. Patient no 3 had lost donor‐type chimerism at the enf of second months. Patient no 1 and no 2 needed for admission to intensive care unit due to pneumonia and gram negative sepsis, respectively. Patient no 2 died due to gram negative septic shock in the 11th month of allo‐HCST. Unlike others, EBV DNA titer increased to 1978 copy / ml in patient no 2. Without treatment, the EBV DNA titer gradually decreased and reached a limit of &lt;153 copies / ml.Summary/Conclusion:The timing of HSCT for PID diseases in adulthood is considered to be rather late. However, HSCT yet offers a curative potential without causing a serious toxicity due to conditioning regimens and an increased rate of infections during neutropenic period. Patients with intensive history of infection require strong cooperation with intensive care units, infections and chest diseases in the transplantation and post‐transplant follow‐up periods. These patients should be strictly followed‐up for the risk of acute/chronic GvHD. The long term effects of immunosupressive treatment among these patients is also a serious concern.image