Rates accessoires après splénectomie pour thrombopénie immunologique chez un patient ayant un déficit immunitaire commun variable

Introduction

Blood cells are mainly destroyed in the spleen during autoimmune cytopenia. Amongst the various therapeutic strategies, splenectomy is sometimes necessary during the disease course. However, splenosis or accessory spleens can account for autoimmune cytopenia relapse after initial splenectomy in these patients.

Case report

We report an 18-year-old male with common variable immunodeficiency who presented with immunological thrombocytopenia. Splenectomy allowed remission of cytopenia, but a relapse was attributed to splenosis, because Jolly bodies were absent on blood smear. Laparoscopic splenectomy of accessory spleens induced long term remission. A literature review is performed.

Conclusion

Fifteen to 20% of relapses of autoimmune cytopenia treated by splenectomy are related to accessory spleens. Ablation of accessory spleens can cure again the patients, including patients with accompanying common variable immunodeficiency.     

Adult idiopathic thrombocytopenic purpura: Clinical findings and response to therapy

Sixty-two adults with idiopathic thrombocytopenic purpura were seen from 1971 to 1979. All were >16 years old, with < 30,000 platelets/μl and adequate marrow megakaryocytes. None had established systemic lupus erythematosus. Forty women and 22 men had median ages of 49.5 and 35.3 years. At presentation, 10 had a prior malignancy in remission, four were pregnant and four had autoimmune hemolysis. Of 59 patients evaluated for their response to prednisone therapy, 25 (43 percent) had a complete response (platelets > 150,000/μl). In 75 percent of the patients, complete remission was achieved by six weeks. Only 29 percent of those with a complete remission (complete responders) are projected to be in a continuing remission after 48 months. The majority of relapses occurred during the first two years of remission. A symptom duration of < 14 days was associated with a favorable response (p < 0.001). Age, sex, initial platelet count, serology and speed of platelet response were not predictive of the response to prednisone therapy. Thirty-seven patients underwent splenectomy. Twenty-seven (73 percent) had a complete response and nine have subsequently had a relapse. Sixty-one percent of the responders are in a projected complete remission at 48 months with a subsequent flattening of the actuarial remission duration curve. In 80 percent of the patients in whom complete remission was attained after splenectomy, it was attained by the fifth postoperative day. A prior response to prednisone therapy and younger patient age were both positive prognostic factors for the response to splenectomy. Two of eight patients in whom splenectomy failed to achieve a remission (splenectomy failures) responded to additional prednisone therapy. Three of five patients have responded to accessory splenectomy. Eighteen patients have been refractory to all therapy.     

Autoimmune hemolytic anemia associated with ulcerative colitis

Three patients are reported in whom autoimmune hemolytic anemia developed during the course of ulcerative colitis. A review of the literature yielded 11 additional cases, and the clinical, immunologic, and therapeutic characteristics are summarized. The results of steroid therapy and splenectomy are similar to those for idiopathic autoimmune hemolytic anemia. The cause and effect relationship between these two diseases is not clear, but colectomy appears to produce remission in hemolysis when the latter is refractory to both steroids and splenectomy.     

Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome

Kabuki syndrome (KS) is often associated with autoimmune abnormalities, such as idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, leukoplakia and thyroiditis, as well as congenital anomalies. We herein present a KS patient with refractory ITP who achieved durable and complete remission in response to a total of four once-monthly infusions of rituximab. KS patients are often more susceptible to infection, so splenectomy should be avoided. Therefore, rituximab therapy is an alternative option for KS patients with ITP who fail to respond to first-line therapy.     

Long-term outcomes in adults with chronic ITP after splenectomy failure

Adult chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder manifested by thrombocytopenia from the effects of antiplatelet autoantibodies and T lymphocyte-mediated platelet cytotoxicity. Multiple studies show that corticosteroid treatment and splenectomy, alone or together, increase platelet counts to safe levels in 60% to 70% of patients. However, there is little information on the outcomes of ITP patients refractory to splenectomy. We studied 114 patients with ITP for whom splenectomy failed and who required additional therapy; long-term follow-up was available on 105 (92%) patients. Seventy-five (71.4%) patients attained stable partial (platelet count greater than 30 x 10(9)/L) or complete (normal platelet count) remission; 51 patients remained in remission after therapy was discontinued, whereas 24 patients required continued treatment. Median time to remission after splenectomy failure was 46 months (range, 1-437 months). Median remission durations were 60 months (range, 10-212 months) for patients off therapy and 48 months (range, 2-167 months) for patients on therapy. Thirty (29.6%) patients remained unresponsive to treatment. Thirty-two patients died, 17 (15.7%) of ITP (bleeding, 11 patients; therapy complications, 6 patients) and 15 (13.9%) of unrelated causes. We conclude that most patients with refractory ITP attain stable remission, though on average this occurs slowly. However, a subpopulation with severe, resistant disease experiences significant morbidity and mortality.     

The value of platelet-associated IgG in predicting the efficacy of splenectomy in autoimmune thrombocytopenia

In a prospective study, the hypothesis of whether the quantitative determination of platelet-associated IgG (PAIgG) in patients with chronic autoimmune thrombocytopenic purpura (ATP) can predict the efficacy of splenectomy, was investigated. PAIgG levels were repeatedly determined in 16 patients with definite ATP pre- and postsplenectomy, and related to platelet counts and platelet mean life span. It was found that patients with an immediate remission after splenectomy tended to have lower PAIgG levels (less than 6%) than failures, but this difference was not statistically significant. We conclude that PAIgG is of limited value for the prediction of the efficacy of splenectomy in ATP.     

Allogeneic stem cell transplantation for Evans syndrome.

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.     

Autoimmune thrombocytopenic purpura after autologous stem cell transplantation

The pathogenesis of thrombocytopenia occurring after autologous stem cell transplantation (ASCT) remains unclear. Six cases of classical peripheral thrombocytopenia that developed after ASCT for non-Hodgkin's lymphoma (NHL) are presented. Resolution of this complication was obtained by usual treatment such as steroids, splenectomy or progressively resolved without specific treatment. Five out of six patients have been followed for more than 5 years after hematopoietic transplantation and are still alive in complete remission despite poor prognostic factors at diagnosis. Several arguments suggest that this phenomenon represents autoimmune thrombocytopenia and may be the consequence of an altered immune balance. Consequently, development of autoimmune reactions after bone marrow transplantation might be associated with an antitumoral effect (graft-versus-lymphoma effect).     

Thrombotic risk in patients submitted to splenectomy for systemic lupus erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia

Background: Splenectomy has been performed to treat refractory autoimmune thrombocytopenia. However, some reports have suggested that an increased risk of thrombosis could be present in splenectomized patients. This study aims to evaluate the possibility of an increased risk of thrombosis after splenectomy in patients with systemic lupus and antiphospholipid syndrome. Methods: Thrombotic-related events in patients with systemic lupus erythematosus (SLE) and/or primary antiphospholipid syndrome (PAPS), before and after splenectomy for severe thrombocytopenia, were compared. Clinical data, laboratory investigations, and anticoagulation or antiaggregation treatment data were collected from the notes of outpatients attending three European centers. Results: Twenty patients who had had a splenectomy were identified: eight with SLE, five with PAPS, and seven with SLE and APS. The mean time between diagnosis and splenectomy was 3.1 years and mean follow-up was 6.5 years. There were no differences in anticardiolipin antibody titers, lupus anticoagulant, anti-DNA or anti-nuclear antibodies before and after surgery. The incidence of venous events before and after splenectomy was not significantly different. There was a trend towards an increase in the total number of arterial events post-splenectomy. In aCL-positive patients, and in the pre-splenectomy period, the total number of miscarriages was higher (p=0.017), as was the number of patients who had had a miscarriage (p=0.025). Conclusions: The total risk of thrombosis in patients with PAPS and SLE was not increased after splenectomy, but there was a trend towards an increase in the number of arterial events. Splenectomy induced long-term remission of thrombocytopenia (partial or complete) in all patients.     

Two cases of refractory warm autoimmune hemolytic anemia treated with rituximab

Autoimmune hemolytic anemia is thought to be mediated via auto-antibodies produced by lymphoid B cells. This may be an idiopathic process or secondary to an underlying infection or lymphoproliferative disorder. Conventional treatment comprises immunosuppression with corticosteroids and, in some cases, splenectomy. A proportion of patients require lifelong immunosuppression to maintain disease remission. Monoclonal antibody rituximab has gained widespread acceptance in the management of B-cell malignancies. Additionally, it has been used to treat disorders associated with auto-antibody production, such as cold hemagglutinin disease, immune thrombocytopenia, and Evans syndrome. Its use in the treatment of patients with autoimmune hemolytic anemia in the setting of allogeneic bone marrow transplantation as well as in patients with an underlying lymphoproliferative disease has also been reported. We report herein the successful use of rituximab in the treatment of two patients with idiopathic refractory warm autoimmune hemolytic anemia, who are still in remission at 15 and 9 months following treatment.     

Rituximab for warm-type idiopathic autoimmune hemolytic anemia: a retrospective study of 11 adult patients

Warm-type idiopathic autoimmune hemolytic anemia (AIHA) is a relatively common hematologic disorder resulting from autoantibody production against red blood cells. Steroids represent the first-line therapeutic option, and immunosuppressive agents as well as splenectomy are used for refractory cases. Recently, the anti-CD20 monoclonal antibody rituximab has been shown to control autoimmune hemolysis in patients with refractory chronic disease. We report results from a retrospective analysis of 11 adult patients receiving rituximab for steroid-refractory AIHA of the warm type at a mean age of 55 yr (range 23-81 yr). All patients were given methyl-prednisolone as first-line treatment and some of them also received azathioprine and intravenous high-dose immunoglobulins. One patient underwent splenectomy. All patients were considered refractory to steroids and/or immunosuppressive drugs and all were then given weekly rituximab (375 mg/m(2)) for four consecutive weeks. An increase in hemoglobin (Hgb) levels in response to rituximab, with a mean increment of 3.3 g/dL (95% CI 2.1-4.4), was observed in all cases. Four patients required packed red cell transfusions before starting rituximab and all became transfusion-free. At a mean follow-up of 604 d (range 30-2884 d) since the treatment of AIHA with rituximab, all patients are alive, eight (73%) of them in complete remission (CR) and three (27%) in partial remission (PR). A moderate hemolysis still persisted in six (54%) patients. In conclusion, our experience clearly demonstrates that anti-CD20 monoclonal antibody rituximab is an effective and safe alternative treatment option for idiopathic AIHA, in particular, for steroid-refractory disease.     

Relationship between portopulmonary hypertension and splenectomy: Mayo Clinic experience and review of published works

Aim

Portopulmonary hypertension is a serious complication of portal hypertension that can lead to right heart failure and death. To our knowledge, an association between portopulmonary hypertension and prior splenectomy has not been described previously. The goals of this study were to describe the frequency of splenectomy in portopulmonary hypertension and compare selected parameters between portopulmonary hypertension subgroups.

Methods

This is a retrospective analysis of patients diagnosed with portopulmonary hypertension between 1 January 1988 and 30 June 2015 at Mayo Clinic (Rochester, MN, USA). We compared age, sex, right ventricle systolic pressure by echocardiography, and right heart catheterization measurements/calculations among subgroups of portopulmonary hypertension patients with splenectomy and/or autoimmune liver disease (autoimmune hepatitis/primary biliary cirrhosis/primary sclerosing cholangitis).

Results

The cohort consisted of 141 patients, of whom 8 (6%) had a history of splenectomy prior to the development of portopulmonary hypertension. Twenty‐seven (19%) portopulmonary hypertension patients had autoimmune liver disease, and 5 of 8 (62.5%) splenectomized portopulmonary hypertension patients had autoimmune liver disease. No significant difference was noted in right heart catheterization measurements/calculations between splenectomized and non‐splenectomized portopulmonary hypertension patients. Right ventricle systolic pressure by echocardiography was significantly higher in those splenectomized.

Conclusions

Prior history of splenectomy in portopulmonary hypertension was 6% in this cohort. The combination of autoimmune liver disease and splenectomy in portopulmonary hypertension was not uncommon. History of splenectomy in patients with portal hypertension and/or autoimmune liver disease may have clinical implications.     

Durable complete remission of macroglobulinemia after splenectomy: A report of two cases and review of the literature

Two patients with macroglobulinemia (monoclonal lgM in the serum) and massive splenomegaly were incapacitated by progressive disease refractory to standard chemotherapy. In each case, palliative splenectomy was followed by a prompt, complete, and unexpected clinical remission with disappearance from the serum of the monoclonal IgM component. One patient remains free of disease 12 years after splenectomy. The other patient remained free of detectable macroglobulinemia for 13 years after splenectomy. A review of the literature revealed other cases of remission of macroglobulinemia attributable to splenectomy alone. Data in humans and animals suggest that the spleen may facilitate IgM secretion by normal and malignant B lymphocytes. Splenectomy should be considered a possible treatment option for patients with massive splenomegaly and macroglobulinemia who progress on chemotherapy. © 1995 Wiley-Liss, Inc.     

Vincristine-loaded platelet infusion for treatment of refractory autoimmune hemolytic anemia and chronic immune thrombocytopenia: rethinking old cures

We report our experience with vincristine-loaded platelet infusion in patients with refractory immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome. Ten patients with symptomatic thrombocytopenia and/ or hemolytic anemia who failed to respond to two to six different treatment modalities, including corticosteroids and splenectomy, were treated with infusion of vincristine-loaded platelets. Platelets were harvested by plateletpheresis from a healthy ABO compatible blood donor and incubated with 5 mg vincristine. Excess of vincristine was removed, and platelets were resuspended in 50 ml plasma and infused over 30 min. All 10 patients responded, and 6 of them achieved complete remission. The response was prompt, occurring 3-8 days after vincristine-loaded platelet infusion. Two patients with AIHA are still in remission 9 and 8 years posttreatment with no maintenance treatment. Three ITP patients achieved persisted partial response for 6 years, 5 years, and 11 months; in the remaining 5 patients the response lasted for 2-5 months. No side effects were seen. Our results suggest that this inexpensive and well-tolerated treatment modality may be a useful approach in patients with ITP and AIHA refractory to primary therapy.     

Treatment options for primary splenic low‐grade non‐Hodgkin's lymphomas

The purpose of this comparative study was to evaluate the response of primary splenic low‐grade non‐Hodgkin's lymphomas (NHL) to chemotherapy, splenectomy, and chemotherapy combined with splenectomy in order to elaborate the optimum treatment modality. A total of 104 patients (age range: 15–82 years) with primary low‐grade B‐cell NHL of the spleen were comprised by our study. Stage IV disease was determined in 102 (98.1%) cases. Regarding the treatment modality, splenectomy was performed in 14 patients, early splenectomy and single‐agent chemotherapy in 15, early splenectomy and combined chemotherapy in 19, single‐agent chemotherapy in 23, and combined chemotherapy in 33. In the above‐mentioned order, complete remission rate was following: none, 40.0, 31.6, 21.8, and 18.2%. Partial remissions were achieved in 85.7, 46.7, 57.9, 30.4, and 69.7% of cases, respectively. The median remission duration turned out to be longer (74.5 months) in the group of patients with complete remissions attained by means of splenectomy and combined chemotherapy. Local relapses in the spleen developed in 19 (72.7%) patients treated with combined chemotherapy and in 9 (90.0%), who had undergone single‐agent chemotherapy. The 5‐year overall survival was 54.4% after splenectomy, 39.4% after single‐agent chemotherapy, and 37.1% after combined chemotherapy, being significantly higher (P < 0.05) after splenectomy and single‐agent chemotherapy (67.2%), and splenectomy followed by combined chemotherapy (64.7%). Early splenectomy combined with chemotherapy is the optimum treatment option for primary low‐grade NHL of the spleen because of the superiority in complete remission rate, remission duration, and in overall survival rate. Splenectomy leads to somatic compensation of patients, makes impossible local relapsing in the spleen, prevents continuous dissemination from the primary tumor site, and mostly corrects cytopenias, creating better conditions for chemotherapy.     

Treatment options for primary splenic low-grade non-Hodgkin's lymphomas

The purpose of this comparative study was to evaluate the response of primary splenic low-grade non-Hodgkin's lymphomas (NHL) to chemotherapy, splenectomy, and chemotherapy combined with splenectomy in order to elaborate the optimum treatment modality. A total of 104 patients (age range: 15-82 years) with primary low-grade B-cell NHL of the spleen were comprised by our study. Stage IV disease was determined in 102 (98.1%) cases. Regarding the treatment modality, splenectomy was performed in 14 patients, early splenectomy and single-agent chemotherapy in 15, early splenectomy and combined chemotherapy in 19, single-agent chemotherapy in 23, and combined chemotherapy in 33. In the above-mentioned order, complete remission rate was following: none, 40.0, 31.6, 21.8, and 18.2%. Partial remissions were achieved in 85.7, 46.7, 57.9, 30.4, and 69.7% of cases, respectively. The median remission duration turned out to be longer (74.5 months) in the group of patients with complete remissions attained by means of splenectomy and combined chemotherapy. Local relapses in the spleen developed in 19 (72.7%) patients treated with combined chemotherapy and in 9 (90.0%), who had undergone single-agent chemotherapy. The 5-year overall survival was 54.4% after splenectomy, 39.4% after single-agent chemotherapy, and 37.1% after combined chemotherapy, being significantly higher (P <0.05) after splenectomy and single-agent chemotherapy (67.2%), and splenectomy followed by combined chemotherapy (64.7%). Early splenectomy combined with chemotherapy is the optimum treatment option for primary low-grade NHL of the spleen because of the superiority in complete remission rate, remission duration, and in overall survival rate. Splenectomy leads to somatic compensation of patients, makes impossible local relapsing in the spleen, prevents continuous dissemination from the primary tumor site, and mostly corrects cytopenias, creating better conditions for chemotherapy.     

脾脏切除在长期发热伴脾脏肿大中的诊断价值

目的 探讨发热待查在临床上公有脾肿大供组织学诊断中行脾切除术的价值。方法 回顾分析了我院血液科1996年来以发热待查收住院，除发热、脾肿大外无其它阳性体征，且辅助检查也为阴性的14例患者的临床资料，行脾切除术后取脾脏作病理学检查。结果 14例患者中，霍奇金淋巴瘤3例，非霍奇金淋巴瘤5例，结缔组织病3例，恶性组织细胞病2例，脾陈旧性梗死1例。随访15－54个月，3例结缔组织病完全缓解；1例脾陈旧性梗死痊愈；淋巴瘤3例完全缓解，1例部分缓解。结论 发热待查而临床上仅有脾肿大时，应动员患者尽早地作诊断性脾切除术并送病理学检查，以免延误诊断和治疗。     

Approach to the investigation and management of immune thrombocytopenic purpura in children

Childhood immune thrombocytopenic purpura (ITP) is typically a benign, self-limiting disorder occurring in young (<10 years of age) previously healthy children. More than 80% of such children enter a complete sustained remission within a few weeks to a few months of initial presentation, irrespective of any therapy given. The major concern is the small but finite (0.1 to 0.9%) risk of intracranial hemorrhage, which occurs in children with very low platelet counts (<20 x 10(9)/L), and is the justification for treatment to increase the circulating platelet count. Effective treatment strategies are single-dose intravenous immunoglobulin G (IVIgG; approximately 1 g/kg) and medium to high-dose corticosteroids, administered orally or parenterally. The necessity for initial bone marrow aspiration and hospitalization continues to be debated. In children with chronic ITP, defined by persistence of thrombocytopenia for > or =6 months, splenectomy should be considered for the relatively small subgroup with symptomatic, severe thrombocytopenia who have either failed an adequate trial (> or = 12 months) of primary therapy (IVIgG, intravenous anti-D, corticosteroids) or are intolerant of such therapy. Laparoscopic splenectomy is preferred over open splenectomy. Children who fail to respond to splenectomy ( < or = 20% of cases) should be evaluated for the presence of accessory spleens; their management is often difficult and must be individualized. In severe refractory cases, second-line therapies (such as azathioprine or vinca alkaloids) need to be considered. Secondary ITP in children is relatively rare and is sometimes associated with other autoimmune cytopenias (Evan's syndrome, ITP with autoimmune neutropenia). These cases often respond poorly to conventional medical therapies and response rates to splenectomy are considerably lower than in children with primary chronic ITP.     

Laparoscopic splenectomy for autoimmune hemolytic anemia in patients with chronic lymphocytic leukemia: a case series and review of the literature

The purpose of this study was to evaluate the safety and efficacy of laparoscopic splenectomy in patients with chronic lymphocytic leukemia (CLL) complicated by autoimmune hemolytic anemia. A series of nine such patients who underwent this procedure at our institution between August 1997 and September 2001 were retrospectively reviewed. Seven of 9 patients who underwent laparoscopic splenectomy for CLL and autoimmune hemolytic anemia achieved a complete response. One patient who initially responded relapsed 12 weeks postoperatively. Therefore, six of 9 patients showed sustained responses with a mean follow-up of 2 years, consistent with other published series. Two patients had no response, one of whom died within 3 weeks of surgery from transformed Hodgkin's disease. The only other postoperative complication occurred in a patient who developed pneumonia. We conclude that laparoscopic splenectomy is a safe and effective treatment for autoimmune hemolytic anemia in patients with CLL who fail medical therapy.     

Autoimmune hemolytic anemia and common variable immunodeficiency: a case-control study of 18 patients

To describe the main characteristics and treatment of autoimmune hemolytic anemia (AHA) in patients with common variable immunodeficiency (CVID), we analyzed data from 18 patients, 4 from an earlier study and 14 from the French DEF-I cohort on adult patients with primary hypogammaglobulinemia. To be included, patients had to have CVID and a previous history of AHA with a hemoglobin level < or =90 g/L at onset. To determine whether AHA is associated with a particular clinical phenotype of CVID, we conducted a case-control study from the DEF-I cohort.The estimated frequency of AHA in CVID patients from the DEF-I cohort was 5.5% (14/252). Median age at AHA diagnosis was 26 years (range, 1-57 yr), and 27.5 years (range, 5-61 yr) at CVID diagnosis. CVID was diagnosed before the onset of AHA in only 2 patients (11%). CVID was diagnosed more than 6 months after AHA in 10 cases (55.5%), and the 2 conditions were diagnosed concomitantly in 6 cases. The 14 patients included in the DEF-I cohort were compared with 238 control patients with CVID but without AHA.Corticosteroids were used as initial treatment for all patients in the current study. An initial response was obtained in 15 of 18 (83%) patients. Overall, 9 of these (60%) achieved a lasting response with steroids alone (7 patients) or in combination with intravenous immunoglobulin (2 patients). Seven patients underwent splenectomy, and 5 additional splenectomies were performed for associated autoimmune thrombocytopenic purpura. After splenectomy, a lasting response was obtained in 3 of the 7 patients with AHA. However, 5 of the 12 splenectomized patients experienced life-threatening infection. Severe infection occurred in 2 of 4 patients receiving immunosuppressive drugs. At the end of follow-up, 13 of 18 (72%) patients were in treatment-free remission (13 complete responses), and 4 of 18 (22%) were in remission while on prednisone < or =20 mg/d. One patient had died, of cancer.