Secondary Hypogammaglobulinemia Research Articles

Immunoglobulin G treatment of secondary immunodeficiencies in the era of novel therapies.

The demonstration of poor vaccine responses, together with low immunoglobulin (Ig) levels, are the mainstay of clinical diagnosis of antibody deficiency requiring IgG replacement therapy (IgGRT) 1. Hypogammaglobulinaemia refers to the finding of low Ig levels in the blood and acts only as a surrogate marker for antibody deficiency. In general, secondary antibody deficiencies caused by different immunomodulatory treatments are poorly studied. This is especially true with regard to systematic assessment of serological vaccine responses to T dependent protein and T independent polysaccharide antigens in patients with secondary hypogammaglobulinaemia. Although the backbone of most immunomodulatory regimens includes glucocorticoids, the effects of glucocorticoids on polysaccharide responses are insufficiently known. This causes further difficulties in differentiating primary and secondary antibody deficiencies from each other 2. The best-studied secondary antibody deficiencies are those found together with lymphoproliferative malignancies. Compared to historical controls, IgGRT has been shown to increase primary antibody deficient patients' life expectancy by more than 30 years 3. With the increasing use of cytotoxic and biological therapies against lymphoproliferative and autoimmune diseases and in organ transplantation, secondary immunodeficiencies with symptomatic hypogammaglobulinaemia are seen more commonly 4,5. The available studies on IgGRT in chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM) have recruited small numbers of patients and were performed mainly more than 20 years ago. Modes of chemotherapy used then differ greatly from contemporary treatment. Furthermore, the overall prognosis was much poorer, follow-up times in the studies were short and, unsurprisingly, no effect on overall survival was shown. There are even fewer available data on substitution therapy in lymphoma survivors with hypogammaglobulinaemia, although newer anti-CD20 therapies may have increased their incidence. Surprisingly, although long-term glucocorticoids have been used for decades, we also have insufficient knowledge on the exact magnitude and duration of suppression of vaccine responses and of Ig production caused by glucocorticoids. The available data on symptomatic hypogammaglobulinaemia and IgGRT in patients with CLL and MM following lymphoma treatment and in autoimmune diseases are reviewed.

Serum free light chains in the differential diagnosis and prognosis of primary and secondary hypogammaglobulinemia

Serum free light chains in the differential diagnosis and prognosis of primary and secondary hypogammaglobulinemia

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia

BackgroundAlthough secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia. MethodsThis retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia). ResultsAmong the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group. ConclusionsThough mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.

Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders.

The role of IgM-enriched intravenous immunoglobulin in transplantation

After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG) which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.

A Case of Prolonged Hypogammaglobulinemia after Rituximab-Containing Chemotherapy in a Patient with Lymphoma

Rituximab, an anti-CD20 monoclonal antibody, is an effective target agent against the B lymphocytes in B-cell lymphoid malignancies and various lymphoproliferative diseases. Moreover, the toxicity of rituximab is less severe than that of conventional cytotoxic agents, which has promoted the widespread application of rituximab in the treatment of B-cell lymphoma. However, depletion of B lymphocytes by rituximab, which leads to secondary hypogammaglobulinemia, can cause deterioration of humoral immunity. Although immune reconstitution after hematopoietic stem cell transplantation is known to prevent prolonged hypogammaglobulinemia, very few cases of long-standing hypogammaglobulinemia have been reported. We report herein a case of prolonged hypogammaglobulinemia after rituximab-containing chemotherapy and splenectomy in a patient with non-Hodgkin`s lymphoma and discuss the clinical significance and pathogenetic mechanism of this phenomenon with a literature review. (Korean J Med 2014;87:357-362)

P-001 Crohn’s-like Disease in a Patient with Good Syndrome

There has been described a Crohn’s-like disease in patients with congenital immunodeficiency syndromes (chronic granulomatous disease, glycogen storage disease type Ib, common variable immunodeficiency…). We report a case of a Crohn’s-like colitis and perianal fistula in a patient with Good Syndrome, an acquired immunodeficiency. A 58 years old male, was diagnosed in January 2004 of thymoma and secondary hypogammaglobulinemia (Good Syndrome). He was treated by thymectomy and radiotherapy. Eleven months later the surgery, the patient developed bloody diarrhea, colicky abdominal pain, fever, weight loss and complex perianal fistula. In physical exam, abdomen exploration was not remarkable; there was a perianal fistula with fecal and purulent drainage. The laboratory findings were: hemoglobin 12.4 g/dL, platelets 70 × 10^9, CD4 293 cells/μL, CD3 and CD8 were normal, ratio CD4/CD8 0.34, IgA 14 mg/dL and IgM 5 mg/dL. The rest of results were normal. A colonoscopy was carried out finding multiple superficial ulcers in rectum, sigma, left colon and cecum. Transverse, right colon and ileum were unaffected. Biopsies showed nonspecific moderate inflammatory infiltrate of lymphocytes and plasma cells. No granulomas, crypt abscesses or CMV inclusions were found. Fecal cultures were all negative. Finally a probability diagnosis of Crohn’s disease was done and the patient was treated with mesalazine, steroids and metronidazole without any improvement. Monthly IV immunoglobulins were also administered. Thiopurines and anti-TNF were not used because of recent diagnosis of thymoma. During the following 5 years progressive pancytopenia was developed and recurrent fungal, bacterial and viral infections occurred including a septic shock. Finally the patient died in February 2009 because of E. coli septicemia. Thymomas represent 0.2%–1.5% of malignant neoplasias; 3%–6% of them develop hypogammaglobulinemia after the surgery, what it is called Good syndrome. This acquired immunodeficiency is both cellular and humoral; Immunoglobulins are absent or very low and CD4 are low with a CD4/CD8 ratio <1. The patient suffers different recurrent and opportunistic infections; being the general survival 4 years. There is no specific treatment despite IV immunoglobulins therapy. A Crohn’s-like disease has been reported in other immunodeficiency syndromes (as a chronic granulomatous disease, glycogen storage disease type Ib or common variable immunodeficiency). Our patient had a phenotypically Crohn’s disease pattern, but biopsy was not specific and he did not have a response after steroids treatment. We hypothesize that this patient had a Crohn’s-like syndrome similar to those have been reported in other immunodeficiencies. Congenital immunodeficiency syndromes sometimes developed a Crohn’s-like syndrome. - Good syndrome is an acquired immunodeficiency syndrome compromising both cellular and humoral immune response. - We describe a Crohn’s-like syndrome on a patient with Good syndrome, suggesting a similar pathogenic mechanism with congenital immunodeficiency and possibly Crohn’s disease.

Post‐marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections

Secondary hypogammaglobulinemia is one of the factors responsible for the increased susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). This study assessed the therapeutic results, concomitant medication and tolerance of administering 5% intravenous immunoglobulin, secondary immunodeficiency and recurrent serious bacterial infections. A single center, post-marketing, observational clinical study was performed on 10 patients with a variety of hematological malignancies (CLL, follicular non-Hodgkin lymphoma, IgM-secreting immunocytoma, IgA plasmacytoma and myelodysplastic syndrome/non-Hodgkin lymphoma) who had been infused with IVIG from June 1994 to May 2009. The clinical benefit of IVIG was assessed by comparing the incidence of bacterial infections before and after starting this therapy. Plasma immunoglobulin concentrations and relevant hematological variables were recorded. For safety assessment, adverse events were monitored. The standard IVIG dosage was approximately 0.35 g/kg body weight every 3-4 weeks. Most patients had normal IgG trough values of >600 mg/dL during the IVIG treatment period. The rate of bacterial infections was reduced from 2.4 per patient in the 3 months before IVIG to 0.7 (0-1.5) per patient per year during IVIG treatment. All patients received concomitant medication, mainly anticancer and anti-anemia therapy (100%). No serious adverse events related to IVIG were observed. The frequency of at least one minor adverse reaction was 1.44% (8/556 infusions). In conclusion, the investigated IVIG preparation was well tolerated and clinically beneficial in reducing the long term rate of serious bacterial infections in patients receiving concomitant treatment for malignant diseases.

Impact of Non-Fixed Versus 6 Month Fixed Retreatment Schedules on Serum Immunoglobulins Following Rituximab in Patients with Rheumatoid Arthritis

Objectives: To assess the incidence of secondary hypogammaglobulinemia in patients with rheumatoid arthritis (RA) following multiple cycles of rituximab (RTX) related to two different therapy regimens. Methods: 73 patients with RA were retreated using 6 months-fixed strategy and 63 patients using a non-fixed regimen. All received ≥ 2 courses of RTX. Data on serum immunoglobulins (Ig), serious infections and DAS28 were collected, with maximum follow-up being 24 months for the 6 months fixed group and 156 months for the non-fixed group). Statistics for non-parametric analysis were applied. Results: The percentages of patients developing low IgG or IgM did not differ between groups after the 3rd cycle, but those with non-fixed retreatment tended to be higher. After 4 cycles, median IgM levels were significantly lower in both groups compared with pretreatment (p<0.05). Only patients in the fixed retreatment group receiving 4 cycles of treatment showed a significant drop in median IgG level (p<0.05). IgA levels remained within the normal range. Withdrawals due to infections per 100 patient years (py)s in patients with low IgG were higher after 3 Cycles in patients within the fixed retreatment group (4.60/100py vs 1.36/100py, CI: 0.59, 6.23). DAS28 did not differ between cohorts after multiple cycles. Conclusions: Although the percentage of RA patients developing low IgG tended to be higher in the nonfixed group, median IgG level was significantly lower after 4 Cycles of RTX in the fixed regimen group. The fixed retreatment group also had more patients discontinuing rituximab over a shorter period of time (24 months compared with 156 months), with no significant differences in median DAS28 after multiple Cycles. If multiple cycles of RTX are to be instituted, non-fixed regime may allow the opportunity to control the disease with a lower incidence of withdrawal due to low Igs and infections.

Wiederholte opportunistische Infektionbei sekundärem Immunglobulinmangel

Secondary hypogammaglobulinemia may be a relevant predisposing condition in patients with recurrent bacterial upper airway disease (pneumonia, sinusitis) or first-time opportunistic infection, particularly if additional immunosuppressive factors like underlying hematological disease or immunosuppressive therapy are present. As an example, we present a retired farmer with myeloma, treated Hodgkin-lymphoma and hypogammaglobulinemia suffering from the third episode of Rhodococcus equi pneumonia. Screening for hypogammaglobulinemia is recommended in patients with unexplained recurrent bacterial airway infection or first time opportunistic disease, particularly with micro-organisms controlled by humoral immunity. Screening should include the analysis of total immunoglobulin levels (IgA, IgG and IgM). If results are ambiguous, tetanus toxoid and pneumococcal polysaccharide vaccine should be administered with measurement of specific antibody titer before and one month after vaccination. An adequate antibody response largely excludes a clinically significant humoral immunodeficiency. If hypogammaglobulinemia is present in a patient with recurrent or opportunistic infections, periodical substitution of IVIG in a dose and frequency to prevent further infectious episodes should be initiated. This is usually achieved with an IVIG-dose of 0.4g/kg body weight every 3 - 4 weeks to reach a trough IgG-level of 5 - 7g/L.

Improved quality of life with home therapy with subcutaneous immunoglobulins for patients with secondary hypogammaglobulinaemia

Background We reported 10 cases where SCIg turned out to be the preferred route of Ig replacement therapy for patients who developed secondary hypogammaglobulinaemia following bone marrow transplantation or chemotherapy treatment for neoplasia. Patients’ age ranged from 2 to 19 years old, 7 patients being below the age of 10. Six out of the 10 patients were transitioned from IVIg to SCIg: 4 patients due to systemic side effects associated to IVIg perfusions and 2 patients due to poor quality of life related to frequent travels to the hospital for IVIg infusion. Four out of the 10 patients were Ig naive patients and were started directly on SCIg. All patients received a weekly dose of 100mg/Kg infused in two different sites assisted by a battery-powered pump. Patients were given a 1:1 dose when transitioned from IVIg to SCIg. A significant increase of the IgG level was noted in all patients. All patients tolerated very well SCIg therapy with no reported systemic adverse reactions. Local infusion sites reactions were the most frequent observed reactions with a frequency similar to the one observed in patients with primary immunodeficiency disorders (PIDD). Lastly, parents reported improvement in quality of life under SCIg therapy; their child had improved social functioning, better resistance against infections and much improved overall health. Conclusion While home-based SCIg administration relative to hospital-based IVIg has been shown to improve PIDD patients’ quality of life, we believe that SCIg has the potential to improve patient’s satisfaction and independence also in patients with secondary hypogammaglobulinemia.

Treatment of immune thrombocytopenia with intravenous immunoglobulin and insights for other diseases

Since 1946 the development of fractionation and purification methods of human plasma led to biologic immunoglobulin for intravenous use (IVIG). In 1980 a child with refractory immune thrombocytopenia (ITP), bleeding and secondary hypogammaglobulinaemia due to long term immunosuppressive treatment got IVIG. His platelet counts dramatically increased. In 13 consecutive children with ITP, but without hypogammaglobulinaemia, similar rapid platelet increases were observed and confirmed in a controlled, multicentre study. During the past three decades this biologic treatment modality evoked clinical and laboratory research on the mechanisms of action and in disorders with similar immune pathogenesis. It was recognised that IVIG modulates the disturbed immune response in multiple, synergistic ways between the different components of the immune system. Beside other immune hematologic disorders other inflammatory and autoimmune diseases, mainly in the field of neurology and dermatology, IVIG showed beneficial effects. The worldwide consumption of IVIG increased from 300 kg per year in 1980 to 100 tonnes per year in 2010. Due to the heterogeneity of immunopathological mechanisms of autoimmune diseases evidence based indications of IVIG remain rare and off label use high. Registries of large numbers of patients and first endpoints of defining less heterogenous subgroups in immune related disorders are the next steps toward establishment of evidence based IVIG indications.

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post‐transplant antibody deficiency and severe infections

IgG hypogammaglobulinemia is a risk factor for infection in heart recipients. We assessed reconstitution of humoral immunity after non-specific intravenous immunoglobulin (IVIg) replacement therapy administered to treat secondary IgG hypogammaglobulinemia in heart recipients with severe infections. The study population comprised 55 heart recipients who were administered IVIg (IVIg group) and 55 heart recipients with no severe infectious complications (control group). An event was defined as a severe infection requiring intravenous drug therapy during the first year after transplantation. The IVIg protocol comprised non-specific 5% pasteurized IVIg at a dose of 300-400 mg/kg/months. IgG titers were lower in the IVIg group than in controls at seven d (577 vs. 778 mg/dL, p < 0.001) and at one month (553 vs. 684, p = 0.003). After IVIg therapy, IgG concentrations were similar in both groups at three months (681 vs. 737, p = 0.25) and at six months (736 vs. 769, p = 0.46). At three months, the IVIg group had higher levels of antitetanus toxoid and anti-HBs (ELISA, 2.07 ± 2.11 vs. 0.60 ± 1.24 mg/dL [p = 0.003] and 42 ± 40 vs. 11 ± 31 IU/mL [p = 0.005], respectively) than controls. The mean number of infectious complications was significantly lower after IVIG therapy in the IVIG group. IVIg was associated with restoration of humoral immunity in heart recipients with post-transplant IgG hypogammaglobulinemia and severe infections.

Total serum immunoglobulin levels in patients with RA after multiple B-cell depletion cycles based on rituximab: relationship with B-cell kinetics

To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse. CD19(+) B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell depletion therapy. The pattern of B-cell return, either concordant or discordant with relapse, was also recorded. There were 119 responders. Before treatment, three patients had low IgM and four had low IgG. After the first cycle, low IgM or IgG was present in 9.2% (11/119) and 11.8% (14/119) of the patients, respectively, increasing to 38.8% (8/18) and 22.2% (4/18) after five cycles. The mean percent maximum sIg decrease/cycle was relatively constant. The CD19(+) B-cell count at repopulation was not correlated with immunoglobulin (Ig) levels after each cycle. Patients discordant for B-cell return and relapse developed significantly lower serum IgM and more low IgM episodes than concordant patients (P < 0.05). Patients with lower baseline sIg levels tended to develop persistent IgM and IgG hypogammaglobulinaemia, resulting from an accumulation of incremental decreases after repeat cycles. This was not due to lower numbers of returning B cells in those developing low sIgs. The association of low IgM in patients with a discordant pattern of relapse suggests that underlying defects in B cells relating to survival and maturation into Ig-secreting cells, as well as attrition of IgG plasma cells may be contributing to low sIg levels in some patients.

Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus

A nonneutropenic patient with treated low-grade non-Hodgkin's (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.

Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients.

Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n = 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n = 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P = 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P = 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL.

B-cell therapies in established rheumatoid arthritis

B-cell depletion therapy based on rituximab is effective and relatively safe in established rheumatoid arthritis. Rituximab is licensed for the treatment of rheumatoid arthritis in combination with methotrexate and in patients who did not respond or cannot tolerate tumour necrosis factor antagonists. Sustained control of disease activity can be achieved by repeated courses of treatment. The optimal dose and schedule of retreatment are still not established. Nevertheless, data are now available that provide a good base for current clinical practice and a good starting point for further research. In general, rituximab has a good safety profile with most studies showing similar incidences of serious adverse events and infections to placebo. However, reasonable and well-funded doubts remain over the safety of long-term strategies of treatment of rheumatoid arthritis with rituximab, in particular, in relation to the risk of secondary hypogammaglobulinaemia and potential increased risk of infections.

Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil‐treated renal transplant recipients: an emerging clinical phenomenon?

Mycophenolate mofetil (MMF) inhibits T- and B-cell proliferation and can cause acquired or secondary hypogammaglobulinemia. This finding and the subsequent development of opportunistic infection, including pneumonia, have been reported in patients receiving MMF. Chronic pulmonary infection and hypogammaglobulinemia predispose to bronchiectasis, and we aimed to establish the incidence and clinical pattern of this condition within our MMF-treated renal transplant population. We performed a retrospective analysis of MMF-treated transplant recipients. Two hundred and eighty-nine patients were identified and for each, demographic, clinical, radiological and laboratory data from case notes and electronic records were collected. Twenty-three of 289 patients had recurrent severe chest infections (>2 episodes) between 12 and 95 months after the introduction of MMF. The mean age was 53 ± 17yr. Pulmonary lesions fulfilled clinical, radiographic and computerized tomography criteria for bronchiectasis in 7/289 (2.4%). All seven patients with bronchiectasis had low serum IgG levels. Three patients had sufficient samples available for B-cell phenotype analysis but no conclusive results emerged. No cases of post-transplant bronchiectasis were identified in our transplant population not receiving MMF. We report seven cases of bronchiectasis in renal transplant patients receiving MMF. We speculate that low immunoglobulin levels may contribute to the development of this significant pulmonary disease.

175 Humoral Immunity Reconstitution after Intravenous Immunoglobulin Replacement Therapy in Heart Recipients with Post Transplant IgG Hypogammaglobulinemia and CMV Infection

CMV infection remains a cause of death in heart transplantation (HT). IgG hypogammaglobulinemia is a risk factor of this complication. We assessed IgG immune reconstitution after inespecific intravenous immunoglobulin (IVIG) replacement therapy for secondary IgG hypogammaglobulinemia (HGG) in heart recipients with post-transplant CMV infection.

Retrospective Analysis of Weekly Intravenous Immunoglobulin Prophylaxis Versus Intravenous Immunoglobulin by IgG Level Monitoring in Hematopoietic Stem Cell Transplant Recipients

Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n 5 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n 5 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P 5 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P 5 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL. Am. J. Hematol. 87:172–174, 2012. VC 2011 Wiley Periodicals, Inc.