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Prolonged heart allograft survival resulted from donor-specific T-cell sequestering and removal by selective splenectomy in mice.

INTRODUCTION: Selective splenectomy when donor antigen-specific activated T cells are sequestered in the recipient spleen may prolong allograft survival because of removal of all of these T cells. OBJECTIVES: We investigated the effect on cardiac allograft survival in mice by means of removal of activated specific T cells by splenectomy. METHODS: Donor (Balb/c) spleen cells were injected into primed allogeneic recipients (C57BL/6). Selective recipient splenectomy and donor-type cervical heart grafting in Balb/c to C57BL/6 from mice were examined at 0, 24, 48, and 72 hours after donor spleen cell infusion. RESULTS: Control C57BL/6 mice rejected Balb/c heart grafts at 6.86 +/- 0.19 days. Delayed heart grafting plus splenectomy at 24 or 48 hours after donor-type spleen cell infusion significantly prolonged heart allograft survival (24 hours: 15.86 +/- 3.44 days, P < .001; 48 hours: 21.71 +/- 5.22 days, P < .001, respectively). However, 72-hour delayed heart grafting plus splenectomy failed to prevent acute rejection (72 hours: 9.57 +/- 2.51 days, P > .01). Immunohistochemistry showed, at 24 to 48 hours after donor antigen infusion, the recipient spleens characterized by an obvious increase in CD4+ CD8+ T cells in periateriolar lymphoid sheaths, marginal zones, and red pulp compared with the 72-hour group. CONCLUSIONS: Transient accumulation of donor-specific activated T cells in the spleen of recipients provide an opportunity to remove all of these T cells by a surgical procedure. As the largest immune organ the spleen is the main place where T cells are activated and regenerated. At 24 or 48 hours when donor-specific T cells were sequestered in the spleen after donor antigen stimulation, selective recipient splenectomy was able to remove the T cells and prolong was allograft survival. Refinement of this protocol may eventually warrant clinical application.

Animals↗

Laparoscopic and hand-assisted laparoscopic splenectomy for recurrent and persistent ovarian cancer.

OBJECTIVE: Prolonged survival in patients with recurrent ovarian cancer isolated to the spleen has been demonstrated after successful splenectomy. The purpose of this study was to report the outcomes of a series of patients who underwent splenectomy for persistent or recurrent ovarian cancer via laparoscopy or hand-assisted laparoscopy. METHODS: We reviewed the charts of all patients who underwent laparoscopic or hand-assisted laparoscopic splenectomy for presumed persistent or recurrent ovarian cancer. Demographic, clinical, pathologic, and follow-up information was abstracted. RESULTS: Six patients underwent laparoscopy or hand-assisted laparoscopy for presumed ovarian cancer involving the spleen. In 5 of the 6 cases, laparoscopic or hand-assisted laparoscopic splenectomy was successfully performed. For the 5 laparoscopic cases, operative times varied from 155 to 315 min, and estimated blood loss ranged from 50 to 300 ml. There were no perioperative mortalities or significant complications. Hospitalization lasted from 3 to 5 days. Four patients are alive with no evidence of disease at 2-84 months from the splenectomy, while 1 patient died of disease 20 months after the procedure. The sixth patient underwent initial hand-assisted laparoscopy, and the case was immediately converted to laparotomy for resection of peritoneal carcinomatosis. CONCLUSION: Laparoscopic and hand-assisted laparoscopic splenectomies are safe and feasible in the management of patients with presumed persistent or recurrent ovarian cancer. Larger studies are necessary and eagerly awaited to help determine the long-term risks and benefits as well as the most appropriate candidates and selection criteria.

Aged↗

Splenectomy as part of cytoreductive surgery in ovarian cancer.

OBJECTIVE: Epithelial ovarian carcinoma with extensive upper abdominal disease may require splenectomy for optimal tumor cytoreduction. We describe patients who required splenectomy during tumor reduction procedures for primary or recurrent epithelial ovarian carcinoma. METHODS: Data were abstracted from records of 112 patients who underwent splenectomy as part of primary or secondary cytoreductive surgery. RESULTS: Of 112 patients, 66 had primary and 46 had secondary cytoreduction. Some patients also required bowel resection (50%), formal lymphadenectomy (31%), or urinary tract resection (5%). The most common indications for splenectomy were direct metastatic involvement (46%), facilitation of an en bloc resection of perisplenic disease (41%), and intraoperative trauma (13%). Histologically, 65% had hilar involvement; 52%, capsular involvement; and 16%, parenchymal metastases. Short-term complications included wound infections (7), pneumonias (5), thromboembolic events (9), and sepsis (5). Sepsis was associated with an anastomotic bowel leak in 1 patient, with fungal infections in 2 patients (1 pneumonia and 1 pelvic abscess), and with no identifiable infectious source in 2. Two patients required reoperation for bleeding: 1 for diffuse intraabdominal bleeding, including the splenic bed, and 1 for pelvic sidewall bleeding. The perioperative mortality rate at splenectomy was 5%: 3 from sepsis (1 anastomotic leak, 2 pneumonias), 2 from pulmonary embolism, and 1 for which the precise cause of death was not ascertainable. The primary cytoreduction group had a median survival of 1.8 years, with an estimated 2-year survival rate of 46%. The median survival in the secondary debulking group was 1.7 years, with an estimated 2-year survival of 42%. CONCLUSIONS: In patients with clinically significant upper abdominal disease, splenectomy as part of primary or secondary cytoreductive surgery is associated with modest morbidity and mortality. The risk-benefit ratio of aggressive surgical cytoreduction must be considered.

Adult↗

Splenectomy versus medical treatment for idiopathic thrombocytopenic purpura.

BACKGROUND: Treatment strategies for idiopathic thrombocytopenic purpura (ITP) are still uncertain and its management is primarily empirical. The aim of this study was to investigate the role of splenectomy in the therapy of ITP and to evaluate whether medical or surgical treatment is superior. METHODS: Ninety-two patients with ITP were included in the study. All of these patients had medical therapy and 38 of them underwent splenectomy subsequently. Follow-up was completed in 91 patients after a median of 64 months. RESULTS: Side effects of medical therapy were noticed in 32 patients (35%), whereas after surgery only 2 patients (5%) had minor complications. A complete or partial remission was achieved in 35 patients (92%) after splenectomy, whereas this was achieved in only 27 patients (30%) after medical therapy. On multivariate analysis splenectomy and age were the only significant independent factors for complete and partial remission. CONCLUSIONS: Splenectomy is highly effective and safe in the treatment of ITP and is superior over medical therapy. These results should stimulate the discussion about splenectomy for ITP, possibly establishing evidence-based guidelines for surgical treatment in hematology.

Adolescent↗

Comparative analysis of laparoscopic versus open splenectomy.

BACKGROUND: Laparoscopic splenectomy (LS) has been used to treat a variety of splenic disorders. However, there have been few direct comparisons of this approach with open splenectomy (OS). METHODS: Results and outcomes were compared retrospectively in 46 consecutive patients treated by laparoscopic (n = 26) or open splenectomy (n = 20) from January 1990 through March 1996. The two groups were similar in age, sex, and American Society of Anesthesiology classification. Splenectomy was performed for a variety of indications, and the majority of patients in both groups had normal or near-normal size spleens. All data are expressed as mean +/- standard deviation. RESULTS: Laparoscopic splenectomy was successfully completed in all 26 attempted cases. Operative times were significantly longer for LS (202 +/- 55 minutes) than for OS (134 +/- 43 minutes) (P < 0.001); however, operative times in the last 13 LS cases (176 +/- 48 minutes) averaged 51 minutes less than in the first 13 cases (227 +/- 51 minutes). Estimated operative blood loss was less for LS (222 +/- 280 mL) than for OS (376 +/- 500 mL) (P = not significant). A mean of 2.0 units of red blood cells was transfused in 4 (15%) of 26 patients during LS vs 1.0 unit transfused in 2 (10%) of 20 patients who had OS (P = NS). Patients who underwent LS required significantly less parenteral pain medications, had a more rapid return to regular diet, and were discharged sooner than patients who had OS. Complication rates were similar in the two groups. CONCLUSIONS: These results suggest that LS is technically safe and has several advantages over OS. Laparoscopic splenectomy should become the procedure of choice for the removal of normal and near-normal size spleens.

Adolescent↗

Results of laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of immune thrombocytopenic purpura (ITP), hereditary spherocytosis, and Hodgkin's disease. PATIENTS AND METHODS: The study comprised 76 consecutive patients with chronic ITP who were admitted to our hospital from 1968 to 1997 and underwent splenectomy; 35 patients underwent a laparoscopic splenectomy, and 41 had open surgery. RESULTS: Laparoscopic splenectomy involved minimal incision, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.4 versus 3.3); postoperative hospital stay was shorter (9.6 versus 20.1 days, P <0.05). Operative time was significantly longer for the laparoscopic surgery (204.5 versus 99.8 minutes, P <0.01), but blood loss was less (154.4 versus 511.7 g, P <0.01). During the present study (range 3.8 to 80 months), accumulative nonrecurrence rate was 67.9% in 5 years after surgery, which is similar to that of the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy can become an alternative therapeutic modality in the treatment of ITP.

Adult↗

[Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery].

AIM OF THE STUDY: To evaluate the results of laparoscopic splenectomy for hematologic diseases by a multicenter retrospective study. PATIENTS AND METHODS: Between 1991 and 1998, 275 patients (mean age: 40.4 years [18-93]) underwent splenectomy for idiopathic thrombocytopenic purpura (ITP) (n = 209, 76%), for hemolytic anemia (HA) (n = 37) including hereditary spherocytosis (n = 13) and auto-immune anemia (n = 24), lymphoma (n = 12), tumor (n = 6) and uncommon hematologic syndromes (n = 11). Laparoscopic splenectomy was attempted in every patient. The lateral approach was most commonly used with an anterior approach to the splenic hilar vessels, which were cut after hemostasis using a stapling gun; other techniques were also employed. RESULTS: The mean operating time was 165 minutes (45-360); it was shorter in the case of conversion (144 minutes) and became shorter with the operator's experience. Conversion was necessary in 55 patients (20%), due to hemorrhage in 2/3 of cases, related to splenic vessels (20 cases), short gastric vessels (9 cases), or injury of the spleen (8 cases). In ten cases (2%), conversion was necessary for extraction of the spleen. Conversion rate varied from 5.3 to 46.7%, depending on the surgical team. Univariate analysis of factors predisposing to conversion identified four causes: obesity; technique used to achieve hemostasis of the splenic hilar vessels; operator's experience; and presence of splenomegaly. An accessory spleen was found in 44 patients (16%). The weight of the spleen was more than 350 g in 43 patients (15.6%). There were no deaths. There were no significant complications in 236 patients (85.8%) and the mean hospital stay was 6.4 days. In comparison with patients who had a conversion, bowel function returned significantly earlier, use of analgesia was reduced and hospital stay was shorter. The overall morbidity rate was 13.8% (n = 38); morbidity rate was only 10.4% (n = 22) for laparoscopic splenectomy. In these 22 patients, the complications were: subphrenic collections (n = 5, 2.2%), abdominal wall infections (n = 5), thromboembolic events (n = 2), anemia (n = 2), pneumonia (n = 1), peptic ulcer (n = 1), bowel obstruction (n = 1), splenic vein thrombosis (n = 1). Re-operations were required in 4 patients (1.8%) because of hemorrhage, pancreatitis and bowel obstruction. Morbidity rate was significantly increased in the case of conversion (27%), obesity (20%), malignant disease (30%) and splenomegaly (21.8%). Forty-four patients (16%) received perioperative or postoperative blood transfusion and 23 (8.3%) received platelet transfusion. Mean time to return to normal activity was 21 days and was shorter in the absence of conversion (18.5 days versus 35 days). In patients with ITP, the mean platelet count was 240,000 after 3 months, and the failure rate was 8.3%. CONCLUSION: Laparoscopic splenectomy is a real alternative to conventional splenectomy for some hematologic diseases, particularly ITP and HA. The advantages are an uneventful postoperative course, a lower morbidity rate, a shorter hospital stay and an earlier return to normal activity. The limits of this technique are related to the operator's experience, the size of the spleen, the nature of the underlying disorders and patient characteristics, mainly obesity.

Adolescent↗

Should repeated partial splenectomy be attempted in patients with hematological diseases? Technical pitfalls and causes of failure in Gaucher's disease.

BACKGROUND/PURPOSE: The awareness of the risk of overwhelming sepsis after splenectomy prompted surgeons to attempt splenic preservation in patients who had hematologic diseases for which splenectomy was the conventional treatment. Partial splenectomy for Gaucher's disease was widely performed before the introduction of alglucerase. In sporadic cases a second partial splenectomy had also been attempted. METHODS: The authors present three cases of failed repeated partial splenectomy attempted before alglucerase was available. The role of angiography in planning operative strategy and the surgical pitfalls of this unusual reintervention are discussed. CONCLUSION: New indications for partial splenectomy in other hematologic diseases makes the experience gained with Gaucher's disease valuable for management decisions.

Adolescent↗

Laparoscopy improves outcomes for pediatric splenectomy.

BACKGROUND: Pediatric laparoscopic splenectomy is a relatively new surgical procedure with a limited number of reports comparing its outcomes to that of the open procedure. The authors have minimized the invasiveness of our procedure by using only three ports and have described the technique as well as compared it with the open method. METHODS: A retrospective review of seven laparoscopic splenectomies (LS) using a three port technique were compared with seven open splenectomies (OS) performed for similar indications at a single children's hospital. RESULTS: The average age in the LS group was 8.7 years compared with 8.9 years for OS, (P value not significant), and the average weights were also similar. The indications for splenectomy were hereditary spherocytosis, idiopathic thrombocytopenic purpura, sickle cell anemia, and splenic cyst. All splenectomies were performed safely with an average estimated blood loss of 41 mL for LS and 34 mL for OS (P value not significant). Operative time averaged 147 minutes for LS and 86 minutes for OS (P < .05). LS patients recovered more rapidly and were discharged home on a median of postoperative day (POD) 2 versus POD 4 for OS (P < .05). LS patients received significantly less total amount of intravenous pain medication with an average of 0.18 mg/kg of morphine sulfate versus 0.8 mg/kg for OS (P< .05). Total hospital charges were higher for LS with an average of $10,899 versus $8,275 for OS (P < .05). CONCLUSIONS: Laparoscopic splenectomy currently is a safe procedure, offering better cosmesis, much less pain, and a shorter hospital stay compared with the traditional open procedure. The more sophisticated equipment and time needed to carry out the procedure led to a modestly increased hospital cost.

Anemia, Sickle Cell↗

Effect of pretransplant blood transfusions and splenectomy on renal allograft survival in the Lewis rat.

Both pretransplant blood transfusions and pretransplant splenectomy have been shown to improve renal allograft survival in humans and experimental animals. A study was undertaken using the Lewis rat to determine if any combination of pretransplant splenectomy and pretransplant blood transfusions exerted either a synergistic or deleterious effect on renal allograft survival. Pretransplant splenectomy and pretransplant blood transfusions used singly significantly prolonged renal allograft survival. Pretransplant splenectomy followed by 3 blood transfusions also significantly prolonged renal allograft survival. This finding implies that secondary sites of suppressor cell activity, for instance lymph nodes, can be stimulated by blood transfusion and produce prolonged allograft survival in the absence of the spleen. No combination of pretransplant blood transfusion and splenectomy was synergistic. In fact, the group that had pretransplant transfusions followed by splenectomy had allograft survival no different from the control group.

Animals↗

The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura.

The benefits of surgical splenectomy in patients with immune (Idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) Immune globulin (WinRho SDF; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP.

Humans↗

Coloepiploic mobilization during left radical nephrectomy for renal cell carcinoma is indicated to reduce the risk of iatrogenic splenectomy.

OBJECTIVES: To determine whether coloepiploic mobilization (CEM) is indicated to reduce the incidence of iatrogenic splenectomy during left radical nephrectomy for renal cell carcinoma. The incidence of iatrogenic splenectomy during a left nephrectomy is estimated to be between 1.4% and 24%. In a recent study, we reported that the incidence of iatrogenic splenectomy was 8% during a left nephrectomy performed for renal cell carcinoma through a transperitoneal anterior subcostal incision. METHODS: A left radical nephrectomy was performed in 233 consecutive patients for renal cell carcinoma through a transperitoneal anterior subcostal incision with a CEM procedure in which the left colonic flexure was completely detached from the epiploa. Perioperative and postoperative complications, including splenic injury, were noted in a database. The mean patient age was 51.3 years (range 21.3 to 90.2). The mean tumor size was 58 mm (range 15 to 230). RESULTS: An iatrogenic splenectomy was required in 3 patients, and in 1 patient, a splenic injury was treated conservatively. The incidence of iatrogenic splenectomy accompanying left radical nephrectomy was 1.3%. The mean operative time was 120 minutes (range 80 to 240). The mean time to normal gut motility was 3.4 days (range 2 to 11) and to discharge from the hospital it was 9.3 days (range 6 to 19). Regarding CEM, we did not observe any significant abdominal complications. CONCLUSIONS: The incidence of iatrogenic splenectomy during a left radical nephrectomy through a transperitoneal anterior subcostal incision may be reduced by performing the technique of CEM.

Adult↗

[Laparoscopic splenectomy in children: experience and results].

UNLABELLED: Pediatric laparoscopic splenectomy is a relatively new surgical procedure. Advances in instrumentation and technique now make this procedure possible. Splenectomy is frequently performed in children for various hematologic and autoimmune diseases. PATIENTS AND METHODS: This article reviews the indication for splenectomy, the technique of laparoscopic splenectomy and our results. Between January 1996 and January 2000, 23 children underwent laparoscopic splenectomy. Three of them also had a concomitant cholecystectomy. Their ages ranged from three to 14 years. Nine children had hereditary spherocytosis, four were affected by sickle cell disease, three had an idiopathic thrombocytopenia and three a hemolytic disease. One patient was converted. RESULTS: Mean operative time was 170 min (range, 115-230 min). Hospital stay ranged from three to 15 days (median, 6). Five patients had complications (three pneumonia and two deep abscesses). Median follow-up was 20 months (two months to four years) without problems regarding procedure. CONCLUSION: Regarding the low complication rate for this type of patient and the advantages of a small abdominal trauma in the postoperative period, the laparoscopic approach for elective splenectomy in hematological disorders is the technique of choice.

Adolescent↗

Vaccination coverage in adults undergoing splenectomy: evaluation of hospital vaccination policies.

Vaccination coverage in 595 adult patients undergoing total splenectomy in the Hospital Clinic of Barcelona during 1992-2002 was studied. The rates of cover for pneumococcal, Haemophilus influenzae type b and meningococcal vaccines were 63, 63 and 61% respectively, during 2000-2002; 32, 17 and 22% in 1997-1999; and 24, 9 and 8% in 1992-1996. Multivariate analysis showed a greater risk of no vaccination in splenectomies due to trauma, malignant neoplasms of solid organs and incidental splenectomy compared with both neoplastic and non-neoplastic haematological disease, and those patients undergoing splenectomy before 2001. Coverage (>/=1 vaccine) since 1997 in patients with haematological diseases was 83.5% (71/85), haematological neoplasias 69.2% (18/26), solid organ neoplasms 38.3% (36/94), incidental splenectomy 35.6% (16/45), and traumas 28.4% (21/74). Mandatory hospital admission of patients undergoing splenectomy offers a good opportunity for vaccination of these patients. Specific vaccination policies should be developed to take advantage of this circumstance.

Adult↗

Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in patients with advanced gastric carcinoma.

A splenectomy or distal pancreaticosplenectomy is often performed simultaneously with total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. However, the negative impact of splenectomy and pancreaticosplenectomy has also been reported. A retrospective analysis was performed to evaluate the outcomes of distal pancreaticosplenectomy and total gastrectomy, splenectomy and total gastrectomy, and gastrectomy alone in the patients with advanced gastric carcinoma without distant metastasis. Prognostic factors were examined. No significant differences existed in 5-year survival in the patients who underwent gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were prognostic factors. However, distal pancreaticosplenectomy was an independent predictor of pancreatic fistula. In conclusion, the addition of distal pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer increases the risk of severe complications, but does not improve survival.

Aged↗

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia.

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient's immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51+/-6% for group A and 61+/-7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.

Adolescent↗

The response to high-dose intravenous immunoglobulin or steroids is not predictive of outcome after splenectomy in adults with autoimmune thrombocytopenic purpura.

The response to high-dose intravenous immunoglobulin (IVIg) was recently reported to be predictive of outcome after splenectomy in patients with autoimmune thrombocytopenic purpura (AITP). We analysed the records of 75 adults with chronic AITP who received IVIg and subsequently underwent splenectomy. There was no significant difference in the response rate to splenectomy according to whether or not patients had responded to IVIg (81% v 67%, P = 0.36). Age, the time from diagnosis to splenectomy, and the response to steroids were also not significantly associated with outcome after splenectomy. These results indicate that the response to IVIg or steroids is not predictive of the efficacy of splenectomy.

Adolescent↗

Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.

Patients with chronic immune thrombocytopenic purpura (ITP) who are unresponsive to corticosteroids require splenectomy, but if this fails, treatment is difficult. We tried to induce durable remissions in ITP patients refractory to corticosteroids before or after splenectomy by applying strong immunosuppression with the combination of cyclosporin A (CyA 5 mg/kg/d) and prednisone (0.4 mg/kg/d). Patients were assigned to one of two groups. Group 1, 10 patients refractory to prednisone; and group 2, 10 patients refractory to at least prednisone and splenectomy. Overall response rate was 55% (50% in group 1 and 60% in group 2 patients). Nine of the 10 patients in group 1 finally had a splenectomy because of relapse, insufficient response or toxicity of CyA. Thirty percent of the patients discontinued CyA because of side-effects; hypertension, severe headache and muscle pain being the most frequent encountered. It is concluded that CyA treatment does not avoid, but only postpones, splenectomy in chronic ITP patients who are refractory to corticosteroids. However, CyA can be useful in a subgroup of patients with corticosteroid- and splenectomy-refractory ITP, but treatment toxicity is high.

Adult↗