Presence Of Hypogammaglobulinemia Research Articles

Analysis of vaccine responses after anti-CD20 maintenance in B-cell lymphoma in the Balearic Islands. A single reference center experience.

The use of maintenance approaches with anti-CD20 monoclonal antibodies has improved the outcomes of B-cell indolent lymphomas but may lead to significant peripheral B-cell depletion. This depletion can potentially hinder the serological response to neoantigens. Our objective was to analyze the effect of anti-CD20 maintenance therapy in a reliable model of response to neoantigens: SARS-CoV-2 vaccine responses and the incidence/severity ofCOVID-19 in a reference hospital. In our series (n=118), the rate of vaccination failures was 31%. Through ROC curve analysis, we determined a cutoff for SARS-CoV-2 vaccine serologic response at 24 months from the last anti-CD20 dose. The risk of severe COVID-19 was notably higher within the first 24months following the last anti-CD20 dose (52%) compared to after this period (just 18%) (p=0.007). In our survival analysis, neither vaccine response nor hypogammaglobulinemia significantly affected OS. While COVID-19 led to a modest mortality rate of 2.5%, this figure was comparable to the OS reported in the general immunocompetent population. However, most patients with hypogammaglobulinemia received intravenous immunoglobulin therapy and all were vaccinated. In conclusion, anti-CD20 maintenance therapy impairs serological responses to SARS-CoV-2 vaccines. We report for the first time that patients during maintenance therapy and up to 24 months after the last anti-CD20 dose are at a higher risk of vaccine failure and more severe cases of COVID-19. Nevertheless, with close monitoring, intravenous immunoglobulin supplementation or proper vaccination, the impact on survival due to the lack of serological response in this high-risk population can be mitigated, allowing for the benefits of anti-CD20 maintenance therapy, even in the presence of hypogammaglobulinemia.

L’ipogammaglobulinemia che aiuta a spiegare una anemia microcitica di difficile interpretazione

The case of a 3-month-year old child presenting with microcytic anaemia is described. He subsequently developed viral encephalitis. The presence of hypogammaglobulinemia and of a mutation in TRNT1 gene at the genome analysis (NSC) led to the diagnosis of SFID syndrome (sideroblastic anaemia, periodic fever, hypogammaglobulinemia, mental disability).

Patients with Chronic Lymphocytic Leukemia Have a Very High Risk of Ineffective Response to the BNT162b2 Vaccine.

Patients with CLL have high rates of either severe disease or death from COVID-19 and a low response rate after COVID-19 vaccination has been reported. We conducted a single-center study with the main objective to evaluate the immunogenicity of the BNT1162b2 mRNA vaccines in 42 patients affected by CLL with the assessment of antibody response after the second and the third dose. After the second dose of vaccine, 13 patients (30%) showed an antibody response. The presence of hypogammaglobulinemia and the use of steroids or IVIG were the main factors associated with poor response. After the third dose, 5/27 (18%) patients showed an antibody response while in non-responders to the second dose, only 1 patient (4%) showed an elicitation of the immune response by the third dose, with no statistically significant difference. Our data, despite the small size of our cohort, demonstrate that patients with CLL have a low rate of effective response to the BNT162b2 vaccine. However, the effective role of a subsequent dose is still unclear, highlighting the need for alternative methods of immunization in this particularly fragile group of patients.

Management of patients with chronic lymphocytic leukemia during the SARS-CoV-2 pandemic.

Oncohematological patients are prone to develop infections due to immunosuppression caused by the disease and chemo-immunotherapy. The aim of this review was to outline the details of the management of patients with chronic lymphocytic leukemia (CLL) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Patients with CLL often exhibit inadequate humoral and cellular immune responses to various infections and vaccinations. Patients under the ‘watch and wait’ strategy have a lower risk of infections, including with SARS-CoV-2, compared with those undergoing therapeutic interventions, but they still have a higher risk than age-matched controls. Patients with CLL have a high risk of developing severe forms of coronavirus disease-2019 (COVID-19), particularly if they are undergoing chemo-immunotherapy. The total anti-SARS-CoV-2 antibody titer demonstrates a slower increase in patients with CLL infected with the virus, and the antibody levels tend to decrease after reaching a maximum level sooner than in healthy individuals. This leads to a late negativation of the PCR tests and a longer duration of hospitalization. In total, ~1/3 of patients with CLL do not develop a persistent titer of antiviral antibodies, and this is associated with the presence of hypogammaglobulinemia. It appears that patients with CLL have the worst outcomes amongst patients with malignant hemopathies and SARS-CoV-2 infection. Bruton tyrosine kinase inhibitors reduce the hyperinflammatory status of patients with CLL with COVID-19, which is accompanied by decreased levels of serum inflammatory markers, ferritin and D-dimer, and serum levels of pro-inflammatory cytokines, but they increase the risk of infections and impaired humoral immunity. An abrupt discontinuation of these may promote the rapid decompensation of CLL, which may even mimic the clinical manifestations of COVID-I9, including a significant increase in cytokine release. In conclusion, therapeutic decisions must be personalized to each patient with CLL and each at risk patient must be quarantined during the SARS-CoV-2 pandemic to reduce their risk of contraction.

Abstract PO-081: Outcomes of patients with multiple myeloma with COVID-19 infection

Abstract Introduction: While many data have been emerging regarding the outcomes of cancer patients infected with SARS-CoV-2 and their increased risk of mortality, emphasis on patients with hematologic malignancies and how they have been affected during this pandemic is lacking. Louisiana, particularly New Orleans, one of the pandemic epicenters, has a higher-than-average cancer diagnosis rate of multiple myeloma as well as cancer-related deaths. Ochsner Cancer Institute was fortunately prepared for the crisis, which allowed our center to continue taking care of both inpatients and outpatients as needed during the pandemic. Hence, we accumulated ample data among cancer patients and the effects of COVID-19. Here we provide novel initial mortality data on multiple myeloma patients infected with SARS-CoV-2. Methods: Our retrospective, electronic medical record review included 15 patients with a history of multiple myeloma who tested positive for SARS-CoV-2 PCR from March 1st to April 30th, 2020. Medical records were reviewed for inpatient/outpatient status of infection, outcome of infection, multiple myeloma disease and treatment history, and history of autologous stem cell transplant. Results: Out of the 15 patients infected, there were 6 deaths (40%). A total of 11 patients were on active treatment, including all 6 patients who died (54.5%), though active treatment did not appear to be a significant risk factor when compared to off-therapy patients (p=.103). Patients older than 65 years seem to be at increased risk of death when compared to patients less than 65 years of age (p=.011). Hospitalized patients were more likely to succumb to infection compared to non-hospitalized patients (p=.044). Of the 15 patients, 4 had a history of autologous stem cell transplant and this was not found to affect mortality (p=.103). Chronic kidney disease was present in 7 patients and did not appear to impact mortality (p=.315). Of these (n=9), 7 patients had hypogammaglobulinemia and 5 of these patients died (71.4%). Overall, 5 of the 6 patients who died were found to have hypogammaglobulinemia (the 6th death did not have immunoglobulins eligible for review). However, the presence of hypogammaglobulinemia did not appear to increase mortality overall (p=.167). Conclusion: Patients older than 65 years of age with a history of multiple myeloma seem to be at risk of death from COVID-19. Interestingly, a history of autologous stem cell transplant did not appear to affect mortality. While the presence of hypogammaglobulinemia did not affect mortality, its overwhelming finding in the patients who died warrants further discussion in the future. Larger studies are needed to expand on these findings and uncover further characteristics to help stratify at-risk patients in the future. Citation Format: Michael John Lunski, Karine Tawagi, Diana Maslov, Laura Finn. Outcomes of patients with multiple myeloma with COVID-19 infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-081.

Impact of Serum Immunoglobulin Subsets and Levels on Chronic Lymphocytic Leukemia Natural History: A Retrospective Multicentric Italian Experience

Introduction: Chronic Lymphocytic Leukemia (CLL) is a clinically and biologically heterogeneous disorder that can be associated with immunological dysregulation. Several prognostic factors, such as IGHV status and chromosomal aberrations as trisomy 12, del11q, del13q or del17p have been detected so far. More recent genetic mutations, such as BIRC3, SF3B1, NOTCH1 and TP53 stratify even further the prognosis and the outcome in CLL patients (pts). However all data above reported, because of expensive techniques and experience typical of big laboratories, are not available to all medical centers. Therefore we considered necessary to identify more accessible and easy to perform parameters in all laboratories, as data concerning the presence of hypogammaglobulinemia, IgM or IgG monoclonal gammopathy, whose prevalence and impact on natural history of CLL in the medical literature are controversial, contradictory and not very significant because of few numbers in cohorts. Therefore the first aim of the study was to evaluate the prevalence of monoclonal IgM/CLL, IgG/CLL and hypogammaglobulinemia compared with CLL pts with normal immunoglobulins (Ig) levels and to establish the impact on clinical outcomes based on Ig levels. The second aim was to find a correlation between each group of pts and biological data. Methods: From four different Italian centers, we collected data from 1505 pts diagnosed with typical CLL from 1987 to 2017 and we divided them in four groups based on the presence of qualitative and quantitative alterations of serum immunoglobulins. Baseline assessment and levels of serum Ig, immunofixation, chromosomal aberrations and clinical features were collected. [Table 1]. We evaluated the impact of each immunoglobulin subset on progression free survival (PFS) and overall survival (OS). Results: Once assessment was made, we included in our study 1505 pts. Median age of 65.5 was similar in all groups and data gathered from the four centers showed an overlapping rate about prevalence and time-dependent parameters in CLL pts and their related subclasses. The overall prevalence of monoclonal gammopathy was 15%, of whom 149 pts (10%) with IgG/CLL and 73 pts (5%) with IgM/CLL. Hypogammaglobulinemia was detected in 200 pts (13%), while 1083 pts (72%) had no evidence of paraprotein or hypogammaglobulinemia. The worst outcome group was identified among CLL with IgM paraprotein; moreover, this group of pts showed more advanced stages at diagnosis according to Binet staging (p<0.002) and a higher frequency of del17p with a percentage of 15% (p<0.022). [Table 1]. The worse median PFS observed was in IgM/CLL group, compared to Hypogamma/CLL, IgG/CLL, and normal/CLL: 33, 54, 62, 96 months respectively (p<0.0001). At the same time, a projection at 150-months showed an estimated OS of 62% in IgM/CLL group, versus 68% in hypogamma/CLL, 81% in IgG/CLL and 86% in normal/CLL (p<0.0001). To evaluate if the specific deficit of IgG or IgM could have any unfavourable impact on each group's prognosis, we measured the serum levels of IgM and IgG in all pts. No statistically significant differences were observed among time-dependent parameters in IgG/CLL, IgM/CLL and hypogamma groups, based on IgM and IgG levels, if deficient or normal.Finally, in the group of pts who had normal gamma-level, median PFS and TTT was reached at 79 months (p=0.006 and 0.002, respectively) in the subgroup with IgM deficiency, while no statistical difference was observed regarding OS (p=0.785). Conclusions: Our study provides data about prevalence and impact of monoclonal gammopathy and hypogammaglobulinemia on the outcomes of CLL patients. In this study, we observed that the 28% pts had any qualitative or quantitative immunoglobulins alteration, of whom 15% had monoclonal gammopathy and 13% had hypogammaglobulinemia. The worst outcomes were observed in the IgM/CLL pts in terms of PFS and OS. In conclusion, the laboratory data of serum Ig could be used as predictive markers of clinical outcomes because, for their easy availability, they could direct the prognosis of CLL pts. As a future perspective, we would like to characterize pts with monoclonal IgM component from a biological view, to correlate the subset of somatic mutations of the heavy chains of surface immunoglobulins with the monoclonal component and its prognostic significance. Disclosures Varettoni: ABBVIE: Other: travel expenses; Roche: Consultancy; Gilead: Other: travel expenses; Janssen: Consultancy. Trentin:ABBVIE: Honoraria, Other: board; Janssen: Consultancy, Honoraria, Other: Board; gilead: Consultancy; Roche: Honoraria, Other: Board.

1084P - Splenic marginal zone lymphoma: Clinical characteristics and prognostic factors in a series of 52 patients

BackgroundSplenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy, with no standard treatment other than splenectomy. The aim of this retrospective single-center study was to evaluate the clinical characteristics and prognosis of SMZL. MethodsBetween 2008 and 2015, we analyzed a total of 52 patients being considered as appropriate diagnostic criteria for SMZL in our hematology clinic. There were 36 (69%) female and 16 (31%) male patients. Median age was 58.8 years (range, 37-88 years). The median time of follow-up was 20.3 months (range, 3-97.7 months). ResultsWe retrospectively assessed 52 patients from single center, who received splenectomy, either alone or with chemotherapy. The presence of splenomegaly (95.2%) was recorded as the most frequent symptom at diagnosis. Of the patients, 44 (84.6%) had bone marrow involvement and 11 (21.2%) had lymph nodes involvement. Tumor involvement of peripheral blood defined as the presence of absolute lymphocytosis or 5% of tumor lymphocytes in peripheral blood was detected in 10 patients (19.2%). Because of the high frequency of bone marrow involvement, most patients in the series were Ann Arbor stage IV. Data concerning the presence of hypogammaglobulinemia was obtained from only 9 patients (42.9%). Obviously, 20 patients underwent splenectomy. In 7 patients (35%) chemotherapy was received apart from splenectomy.The number of patients reaching clinical complete remission after splenectomy with/out therapy was 18 (90%) and partial remission 3 (15%). The probability of 5 year-overall survival was 87.5%±11.7%. When we analyzed the patients with splenectomy alone the probability of overall survival was 83.3%±15.2%. ConclusionsIn conclusion, although the options of new treatment modality in SMZL have been debated today, splenectomy seems to be safe and effective in controlling long-term disease. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Hypogammaglobulinemia and Poor Performance Status are Predisposing Factors for Vancomycin-Resistant Enterococcus Colonization in Patients with Hematological Malignancies.

Objective:Vancomycin-resistant enterococci (VRE) are common pathogens of hospital-acquired infection. Long hospitalization periods, use of broad-spectrum antibiotics, and immunosuppression are major risks for VRE colonization. We aimed to evaluate patients’ characteristics and factors that may contribute to VRE colonization.Materials and Methods:Data of 66 patients with colonization and 112 patients without colonization who were hospitalized in the hematology clinic were collected. Hematological malignancies, preexisting gastrointestinal complaints, the presence of hypogammaglobulinemia at the time of diagnosis, complications like neutropenic enterocolitis (NEC), and Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance statuses were recorded.Results:Ages of the patients ranged between 19 and 95 years (mean: 55.99). Karnofsky and ECOG scores were statistically related to VRE colonization (p<0.000 and p<0.000), though only the Karnofsky score was significant based on logistic regression analysis. Almost all patients with acute leukemia (45 patients) had been on antibiotics (piperacillin-tazobactam, ceftazidime, and meropenem), while no patients with myelodysplastic syndrome, myeloma, or benign diseases and 2 patients with lymphoma and 1 with chronic myeloid leukemia were on antibiotics. Median time for colonization regardless of antibiotic use and diagnosis was 4.5 days (range: 3-11 days). In the VRE-colonized group, 40.9% of patients had NEC development, while in the non-colonized group, only 1.7% had NEC development. In the VRE-colonized group 46 patients (69.7%) and in the non-colonized group 27 patients (24.1%) had hypogammaglobulinemia at diagnosis; among these patients, 23 patients in the VRE-colonized group (50%) had a B-cell malignancy (lymphoma, myeloma, or chronic lymphocytic leukemia).Conclusion:Besides already anticipated diseases like leukemia, B-cell malignancies are also at high risk for colonization. This proclivity may be attributed to lack of gastrointestinal IgA due to hypogammaglobulinemia. Prolonged hospitalization (>7 days) may also be accepted as a risk factor, independent of diagnosis or antibiotic use. Performance status is also an important factor for colonization, which may be related to poorer hygiene and increased external help.

Good Syndrome Occurred in a Patient a Prolonged Time after Thymectomy: A Case Report and Literature Review of Cases in Japan

A 70‐year‐old Japanese woman was referred to our hospital with productive cough and recurrent respiratory infections. She underwent a thymectomy nine years previously for a thymoma. Based on a three‐year history of repeated respiratory infections and the presence of hypogammaglobulinemia, a diagnosis of Good syndrome was made. We reviewed forty‐six reported Japanese Good syndrome cases. The most commonly infected sites were the lungs, blood, and digestive tracts. Cases with preceding thymoma required a median time of three years (25th and 75th percentile: 1 and 7 years) until hypogammaglobulinemia emerged. The present case showed that Good syndrome should be considered even after a long time period following thymectomy.

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes.

Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival.

Presence of hypogammaglobulinemia and abnormal antibody responses in GATA2 deficiency

Presence of hypogammaglobulinemia and abnormal antibody responses in GATA2 deficiency

THU0515 Hypogammaglobulinemia is a Frequent Finding in Patients Under Immunosuppressive Therapy but Does not Correlate with Susceptibility to Infections

BackgroundAn increased risk of infection is one of the most frequent side effects of immunosuppressive therapy for rheumatic diseases.A decrease in the gamma-globulin serum fraction has been demonstrated in the...

Presence of Hypogammaglobulinemia – A Risk Factor of Mortality in Patients with Severe Sepsis, Septic Shock, and SIRS

In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.

Poor antibody response to pneumococcal polysaccharide vaccination suggests increased susceptibility to pneumococcal infection in splenectomized patients with hematological diseases

Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of pneumococcal infections. Vaccination is a straightforward option in preventing these infections. A well-defined cohort of splenectomized patients with hematological disorders was followed according to response to 23-valent pneumococcal capsular polysaccharide (Pneumovax N ®) vaccination. A total of 76 splenectomized patients (Hodgkin lymphoma, HL 26, non-Hodgkin lymphoma, NHL 19, immune-mediated cytopenias 28, and others 3) with a median age of 52 years (range 18–82 years) were included. Pneumococcal polysaccharide (PS) antibodies were determined using an enzyme-linked immunosorbent assay before vaccination, at peak, and follow-up. A poor response to vaccination was observed in 21 (28%) patients and a good response in 55 (72%), respectively. During the follow-up period of 7.5 years (range 3.5–10.5 years) after vaccination, and despite repeated revaccination in many cases, a total of five episodes (in three patients) of pneumococcal infections were reported, all confined to the poor responder group. Revaccination did not improve antibody levels in this group. The median age at vaccination was significantly higher in the group of poor responders ( p = 0.0006). None of the following factors could predict a poor antibody response: gender, disease activity or aggressiveness in hematological malignancies, previous radiotherapy and/or chemotherapy, time between splenectomy and pneumococcal vaccination, time between chemotherapy/radiotherapy and study pneumococcal vaccination (1 year), or the presence of hypogammaglobulinemia. In conclusion, a substantial proportion of splenectomized patients with hematological diseases mounted a poor PS antibody response and remained at risk for pneumococcal infections despite vaccination. In the absence of apt indirect clinical predictors of antibody response, with the exception of age, measurement of antibody levels seems to be a feasible method for early identification of this patient subgroup. Poor responders do not benefit from revaccination, and should be offered other prophylactic measures.

Aberrant Blood Grouping Results in a Patient with Splenomegaly and Thrombocytopenia

Principal Laboratory Findings [T1] and [T2] Questions: 1. What is (are) this patient’s most striking laboratory result(s)? 2. How do you explain this patient’s most striking laboratory result(s)? 3. What is this patient’s blood group and Rh type? 4. What other tests can be done to confirm this patient’s blood group and the presence of hypogammaglobulinemia? 5. What are other possible causes of ABO discrepancies?