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Extracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12 th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

This report presents updated time-to-event variables from a multicenter phase II trial of reduced-dose 90Y ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL) and mild thrombocytopenia (platelet counts of 100 to 149 x 10(9) platelets/L). Patients received a single course of ibritumomab tiuxetan radioimmunotherapy, with 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (compared to a standard dose of 0.4 mCi/kg). In 30 patients, the overall response rate was 83%, with complete responses (confirmed [CR] and unconfirmed [CRu]) of 47%. Median follow-up time is currently 36.5 months (range: 7.5-54.9+ months). Median duration of response was 11.5 months (range: 1.0-53.9 months), median time to progression was 9.4 months (range: 1.7-54.8+ months), and median time to next lymphoma therapy was 14.6 months (range: 2.3-54.9 months). Median overall survival time has not yet been reached. Long-term responses, defined as time to progression of 12 months or greater, have been seen in 14 of 30 patients (47%) overall, and 12 of 14 CR/CRu patients (86%). Toxicities were primarily hematologic and reversible. No additional long-term adverse events have been observed in the follow-up period, and treatment did not preclude subsequent lymphoma therapies., (Copyright Mary Ann Liebert, Inc.)

This was a 30-patient Phase II trial of reduced-dose (90)Y ibritumomab tiuxetan (Zevalin) RIT for patients with low-grade, follicular, or transformed B-cell NHL and mild thrombocytopenia. Patients were given an imaging dose of (111)In-labeled ibritumomab tiuxetan for dosimetry measurements. One week later, patients were administered a therapeutic dose of 0.3 mCi/kg (11 MBq/kg) (90)Y ibritumomab tiuxetan. Both (111)In- and (90)Y-labeled ibritumomab tiuxetan doses were preceded by an infusion of 250 mg/m(2) rituximab (Rituxan, MabThera) an unlabeled chimeric anti-CD20 antibody, to clear peripheral blood B cells and improve biodistribution of the radiolabeled antibody. For all 30 patients, normal organ and red marrow radiation absorbed doses were well below protocol-defined limits of 2000 cGy and 300 cGy, respectively. Median radiation absorbed doses were 48 cGy to red marrow (range: 6.5-95 cGy), 393 cGy to liver (range: 92-1581 cGy), 522 cGy to spleen (range: 165-1711 cGy), 162 cGy to lungs (41-295 cGy), and 14 cGy to kidneys (0.03-65 cGy). Though most correlative analyses were negative, certain analyses demonstrated a statistically significant correlation between the severity or duration of thrombocytopenia and pharmacokinetic or dosimetric parameters. These correlations were not consistent across the total patient population, and therefore, could not be exploited to predict hematologic toxicity.

We analyzed the efficacy of splenic irradiation in a population of patients with hematologic diseases. The records of the Radiation Oncology Division, Naval Medical Center San Diego were retrospectively reviewed for all patients treated with splenic irradiation (SI) between January 1, 1990 and March 1, 2001. The charts of 17 patients were identified: 5 patients had chronic myelogenous leukemia, 4 had chronic lymphocytic leukemia, 4 had idiopathic myelofibrosis, 2 had polycythemia vera, and 1 patient each had idiopathic thrombocytopenic purpura and acute myelogenous leukemia. Patient ages ranged from 37 to 88 years. Sixteen of 17 suffered from symptomatic splenomegaly. Twenty-six courses of splenic irradiation were delivered to these 17 patients. Treatment courses generally consisted of two fractions of 50 cGy in the first week, two fractions of 75 cGy the second week, and two fractions of 100 cGy the third week. Blood counts were checked prior to each treatment. Seven of the 17 patients died 1 month or less after SI due to the terminal nature of their disease. Twenty-two of 25 treatment courses for splenomegaly resulted in decreased pain and symptoms. Five patients required two treatment courses for splenomegaly, and one patient required five treatment courses. Three of four patients treated for thrombocytopenia demonstrated improvement, but only one was evaluable for more than 2 weeks due to disease-related mortality. Three of five patients treated for leukocytosis had significant improvement. In general, patients suffered few significant complications from this palliative intervention. Splenic irradiation can effectively palliate symptomatic splenomegaly in patients for whom splenectomy is not an option. Retreatment is possible. Splenic irradiation is less effective in the treatment of thrombocytopenia or leukocytosis.

We describe the successful treatment of a neonate with Kasabach-Merritt syndrome who received local irradiation and interferon alpha therapy after failure of corticosteroid treatment. A male neonate, born after an uneventful pregnancy, had a huge haemangioma involving the upper right cervical region as well as severe thrombocytopenia. He was treated with corticosteroids, interferon alpha and radiotherapy. Prednisolone therapy (5 mg kg(-1) day(-1)) was started at 41 days of age. No therapeutic effect was observed after 2 weeks. At this time the tumour size had increased dramatically, platelet counts had decreased progressively and coagulation abnormalities had developed. Because corticosteroid therapy had been ineffective and the child was in a life-threatening condition, irradiation was delivered up to a total dose of 9.5 Gy in five fractions. Simultaneously, prednisolone therapy was slowly decreased and interferon alpha therapy (3 million U m(-2) day(-1)) was started and continued for 6 weeks. After irradiation with 9.5 Gy and beginning interferon alpha therapy, the tumour decreased in size and coagulation parameters normalized within 4 weeks. 6 months later, platelet counts and coagulation parameters were still normal. The tumour had further decreased in size. No acute severe side effects were observed. Radiation therapy combined with interferon alpha treatment is an alternative treatment modality when high dose corticoid steroid therapy has been ineffective in patients with Kasabach-Merritt syndrome, despite the risks of growth delay and secondary malignancy. In children showing no response to corticosteroids, radiotherapy and/or interferon alpha should be considered in Kasabach-Merritt syndrome.

A 21-day-old infant with hemangioma was brought to the hospital with enlargement of the hemangioma of the left thigh and purple discoloration around umbilicus. This led to the diagnosis of Kasabach-Merrill syndrome. Initial treatment with corticosteroid failed. The patient underwent radiotherapy that led successfully to improvement of both hemangioma and thrombocytopenia. After 2 years of follow-up, the patient has experienced long-term complications, including atrophy and growth retardation of the irradiated leg.

Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients., Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia., Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate., Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality.

Systemic unsealed radiation therapy is achieved when a radioactive substance is administered orally or parenterally and that material is concentrated in an organ or site for sufficient time to deliver a therapeutic dose of radiation. The radioactive material usually emits beta particles. In general, there is intense local radiation of the abnormal tissues, and normal organs, which do not trap the radioactive material, are exposed to a small radiation dose. The most frequent treatments involve radioiodine (131)I for hyperthyroidism and differentiated thyroid cancer. Other applications include treatment of painful skeletal metastases, polycythemia vera, malignant cysts, and neuroendocrine tumors. The treatments are usually well tolerated and not associated with long-term effects, such as cancer or infertility.

Purpose: To evaluate our experience in treating patients with HIV-associated thrombocytopenia using splenic irradiation., Methods and Materials: From 1993 to 1998, 10 patients with HIV-related immune thrombocytopenia (ITP) were treated in our department with low-dose splenic irradiation. All patients had either failed more conventional treatment modalities or possessed some contraindication to them., Results: Nine of 10 patients had at least a small, transient rise in their platelet counts, but only two received a substantial therapeutic benefit. Of these two, one died shortly after completing his course of radiation therapy while the other maintained near normal platelet counts up to approximately 3(1/2) years following treatment. There were no treatment-related morbidities and one patient was treated twice., Conclusion: While most patients with HIV-associated ITP may initially respond favorably to splenic irradiation with small rises in platelet count, few responses are likely to be sustained or provide clinically significant outcomes. Our results support those previously reported by others treating this same condition. What remains to be investigated is whether there are any prognostic indicators to help identify those patients most likely to respond to this treatment, thus enabling us to reserve splenic irradiation for those who might derive a substantial benefit from it.

Purpose: To determine the effect of low-dose splenic irradiation on severe Zidovudine-resistant, HIV-1-associated thrombocytopenia (HAT)., Methods and Materials: Between September 1994 and October 1996, 17 patients were included in a prospective study. The patients met the following criteria for inclusion: hemorrhagic symptoms or a platelet count below or equal to 50 x 10(9)/l and normal numbers of megakaryocytes on bone aspiration. The mean baseline platelet count was 20.3 (+/- 14.4) x 10(9)/l; four patients had a platelet count inferior to 10 x 10(9)/l. Splenic volume was defined by ultrasonography. A total dose of 9 Gy was given using an isocentric parallel pair field technique., Results: One month after the end of treatment six patients had a significant rise in their platelet count. Clinically, hemorrhagic symptoms stopped for all patients that were symptomatic. Unfortunately, duration of response was short because for one patient only the platelet count remains stable with a follow-up of 6 months. All patients are alive and in recent evaluation, with four out of eight patients receiving a combination of antiretroviral therapy had a platelet count above 50 x 10(9)/l., Conclusion: Our results are disappointing concerning the duration of response, especially comparatively to those reported in autoimmune thrombocytopenia. Mechanisms of HAT are more complex, and megakaryocytes' infection may play an important role. Splenic irradiation should be considered as palliative treatment for the minority of patients with severe bleeding that does not respond to standard medical treatment.

Splenic irradiation has been used in patients with HIV-related thrombocytopenia. This retrospective review deals with four patients treated with low dose splenic irradiation. All patients had an increase in platelet count and tolerated the treatment without side effects. However, the treatment response lasted for several months only.

Kasabach-Merritt syndrome is the association of thrombocytopenia, spontaneous bleeding, and enlargement of a haemangioma. It is caused by an intense, self-perpetuating process of clot-formation and lysis within the abnormal vascular channels of the haemangioma, and results in consumption of platelets and clotting factors. Treatment involves ablation of the lesion with or without pharmacological manipulation of the coagulation and fibrinolytic systems. No single therapeutic modality is universally successful but a combination of radiotherapy and corticosteroids can result in a dramatic, immediate response with minimal long term complications.

Objective: To determine the role of splenic radiation as a treatment for immune thrombocytopenia., Design: Retrospective analysis of an open, nonrandomized investigation., Setting: A regional cancer center, referred care, and primary care settings., Patients: Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk., Intervention: A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration., Measurements: Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects., Results: Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment., Conclusion: Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high.

We have evaluated 230 patients with myeloproliferative disorders treated in the last 15 years with 32P. None of the patients affected by essential thrombocythaemia developed haematological complications. In the larger group of polycythaemia patients (214 subjects) only 38 patients (17 males and 21 females) developed complications. 60.5% of these subjects had a minor complications: 1.8% showed a thrombocytopenia lower than 100.10e9/lt, 2.3% anaemia with Hb lower than 10 g%, 2.6% leukopenia lower than 40.10e9/lt and 2.3% a pancytopenia. All these complications were transient and eventually treated with limited blood transfusions. We could not identify a correlation between the dose used and the development of such complications. We noted only that the occurrence of anaemia, given a similar dose, was more frequent in females. Only 7% of all patients presented a major complication after 32P administration. In this case too, there was no correlation with the dose administered. Myelofibrosis and chronic myeloid leukaemia resulted to be the more frequent complication (9 out of 15) but we could not clarify if they represented a natural evolution of polycythaemia vera or were due to the treatment with 32P. Acute leukaemia developed only in 5 patients and again we could not recognized a correlation with the dose administered. Moreover, the time from the diagnosis of polycythaemia vera the onset of acute leukaemia ranged widely. 32P has a definite effect on the prevention of thrombotic and haemorrhagic complications in polycythaemia patients since it prolongs their life but it also increases the incidence of acute leukaemia.

Fourteen patients with chronic lymphocytic leukemia (CCL) who received a total of 23 courses of splenic irradiation (SI)for various combinations of painful splenomegaly, progressive leukocytosis, lymphocytosis, thrombocytopenia, and anemia are reviewed. Splenic midplane doses ranged from 200-1750 rads (3-14 days), while the most typicalregimen was 300-450 rads in two to three fractions of 150 rads given over 3-8 days. Response to SI was rated according to a scoring system which evaluated the splenic and hematologic response, as well as the response of disease-related symptons. According to this scoring system, most patients demonstrated a significant relief of painful splenomegaly, along with improvement of hemogram and bone marrow parameters. While those patients judged as failures to prior chemotherapy or total body irradiation showed improvement following SI, those who had received minimal therapy prior to SI showed a superior response. SI, in those showing a satisfactory response, was repeated successfully in several patients (up to six times in one instance). The onset and duration of response to SI, dose-reponse data, survival, clinical and hemotologic responses, and the possible mechanism of action of SI are discussed with reference to the available literature.

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemaglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

This is a retrospective study of 14 patients with lymphosarcoma with hypersplenism. Eight patients received radiation to the spleen followed by splenectomy for recurrence of hypersplenism. Six patients underwent primary splenectomy for hypersplenism. Radiation decreases the size of the spleen but recurrence of hypersplenism is seen in an average of 8 mo. Splenectomy in these cases improves the hematological picture. Average postsplenectomy survival is 27.6 mo. Splenectomy alone in hypersplenism also improves the hematological picture. Postsplenectomy survival in this group is 13 mo. One case of primary lymphosarcoma of the spleen is reported.