Delayed haemolytic transfusion reaction due to anti-M antibody

A female patient with delayed haemolytic transfusion reaction due to anti-M antibody is described. Diagnosis was based on laboratory evidence of haemolysis and on characteristic serological findings. Anti-M was detected in the recipient's serum 7 d after the last transfusion episode. This alloantibody had not been present in the pretransfusion serum. In addition, the direct antiglobulin test was positive on post-transfusion testing and the implicated antibody was eluted from post-transfused red cells.
Delayed haemolytic transfusion reactions have long been recognized as a potencial hazard of transfusion therapy, but such cases due to anti-M are extremely rare.     

Delayed haemolytic transfusion reaction in adults with sickle cell disease: a 5‐year experience

Delayed haemolytic transfusion reactions (DHTR) are potentially life‐threatening complications in patients with sickle cell disease (SCD). Between 1 August 2008 and 31 December 2013, 220 of 637 adult patients in our centre had at least one red blood cell (RBC) transfusion in 2158 separate transfusion episodes. Twenty‐three DHTR events occurred in 17 patients (13 female) including 15 HbSS, one HbSC and one HbSβ⁰ thalassaemia, equating to a DHTR rate of 7·7% of patients transfused. Mean interval from RBC transfusion to DHTR event was 10·1 ± 5·4 d, and typical presenting features were fever, pain and haemoglobinuria. Twenty of the 23 (87·0%) DHTR episodes occurred following transfusion in the acute setting. Notably, 11/23 (47·8%) of DHTRs were not diagnosed at the time of the event, most were misdiagnosed as a vaso‐occlusive crisis. 16/23 DHTRs had ‘relative reticulocytopenia’, which was more common in older patients. Seven of 23 episodes resulted in alloantibody formation, and three caused autoantibody formation. DHTRs are a severe but uncommon complication of RBC transfusion in SCD and remain poorly recognized, possibly because they mimic an acute painful crisis. Most of the DHTRs are triggered by RBC transfusion in the acute setting when patients are in an inflammatory state.     

Hemorrhagic pseudoaneurysm in a patient receiving aflibercept for metastatic thyroid cancer

Background: Agents such as aflibercept, which target the angiogenic pathway, are of great interest as candidates for the management of metastatic differentiated thyroid cancer. Here, we report a patient who developed a hemorrhagic abdominal pseudoaneurysm shortly after being started on this drug. Patient Findings: The patient was a 67-year-old woman being treated with single agent aflibercept (VEGF-Trap) for metastatic thyroid cancer. She had no history of intra-abdominal pathology or vascular disease but had been previously treated with sorafenib. Twelve days after receiving her second dose of aflibercept, she developed vague abdominal pain, which increased in severity and was accompanied by nausea and vomiting. Her symptoms progressed along with a decline in her hematocrit and signs of internal hemorrhaging. An angiogram identified an occluded celiac artery with increased collaterals and a bleeding pseudoaneurysm in the inferior pancreaticoduodenal artery. After the pseudoaneurysm was coiled, the patient stabilized. Summary and Conclusions: Anti-angiogenic agents, usually well tolerated, can disrupt the delicate balance of normal endothelium, leading to hemorrhagic and thrombotic complications. The hemorrhage of aberrant vasculature should be included in the differential diagnosis in patients presenting with vague complaints while being treated with anti-angiogenic agents.     

Delayed haemolytic transfusion reaction in paediatric patients with sickle cell disease: A retrospective study in a French national reference centre

Delayed haemolytic transfusion reaction (DHTR) is a life-threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×10⁹/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke (two patients) and kidney failure (two patients). A further transfusion was required in 23 patients and corticosteroids were used in 21 to reduce the risk of additional haemolysis. In all, 13 patients subsequently received further transfusions with recurrence of DHTR in only two. The study affords a better overview of DHTR and highlights the need to establish guidelines for its management in children.     

Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer

Adoptive transfer of autologous lymphokine-activated killer cells in conjunction with recombinant interleukin-2 in patients with advanced cancer has produced significant regression of metastatic disease in selected patients. We analyzed the effects of interleukin-2 regimens on renal function in 99 consecutive patients. Interleukin-2 therapy with or without lymphokine-activated killer cells was associated with varying degrees of hypotension, fluid retention, azotemia, oliguria, and low fractional sodium excretion. After the patients completed the interleukin-2 regimens, their renal function improved promptly. Renal function values returned to baseline levels within 7 days in 62% of patients, within 14 days in 84%, and within 30 days in 95%. Pretherapy serum creatinine values above 1.4 mg/dL predicted the severity of azotemia and prolonged duration of renal functional recovery, interleukin-2 therapeutic regimens induce prerenal azotemia. Careful selection of patients and early detection of adverse physiologic changes may alleviate the side effects of interleukin-2 therapy.     

Outpatient treatment with subcutaneous interleukin-2, interferon alpha and fluorouracil in patients with metastatic renal cancer: an Australian experience

BACKGROUND: Metastatic renal cell cancer has a poor prognosis and survival. Conventional cytotoxic chemotherapy has no impact on survival and response rates are low. Biologic agents are the most active in treating this disease. We report the feasibility of administering a combination of interferon alpha, subcutaneous interleukin-2 and 5Fluorouracil in the outpatient setting to patients with metastatic renal cell cancer. RESULTS: Between September 1996 and August 2003, fourteen patients were treated with this combination: ten males and four females with a median age of 50 (42-66). Thirteen patients had Eastern Cooperative Oncology Group performance scores of 0 or 1. Ten patients had had nephrectomies. Six patients had undergone prior treatments with chemotherapy or hormonal therapy. Twenty-two cycles were administered (median 1, range of 1-4). Three patients achieved partial response, eight patients had stable disease, and three had progressive disease. The duration of response in patients with stable disease was (3, 3+, 4, 4+, 5+, 6, 10, 11 months) and for the patients with a partial response was 2+, 11 and 12 months. Toxicities with this combination were predictable. There were no treatment-related deaths and no episodes of febrile neutropenia. One patient ceased treatment as a result of toxicity. Fatigue was the most common side-effect. Myalgias, fever and rigors occurred within 6-12 h of administration of interleukin-2, and resolved within 12 h. Grade 1-2 nausea and vomiting occurred in most patients. Four patients had transient asymptomatic transaminitis, which resolved spontaneously. As a result of toxicity, one patient had treatment ceased in his 6th week. CONCLUSION: This combination was feasible, well tolerated and manageable in an outpatient setting.     

A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.     

A phase II trial of dose-intensive interleukin-2 in metastatic renal cell carcinoma

Purpose: High-dose bolus interleukin-2 (IL-2) is currently the sole agent approved by the Food and Drug Administration for the treatment of advanced renal cell carcinoma. This phase II study was designed to evaluate the clinical activity and toxicity spectrum of a regime consisting of dose-intensive IL-2 in both previously treated and untreated patients with advanced renal cell carcinoma. Patients and methods: Twenty eligible, sequential patients received IL-2 at a dose of 24 mIU m⁻²dose⁻¹ (1.33 mg m⁻²dose⁻¹) every 8 h on days 1–5 and 15–19, for a maximum of 28 boluses. Patients achieving stable disease or a response were treated every 10 weeks for a maximum of five cycles/year. Results: Out of 20 study participants 8 patients (40%; 95% confidence interval, 18.5%–61.4%) demonstrated a response. Three of these responses were complete (CR; 15%) while 5 were partial (PR; 25%) and about 75% of the responses occurred in patients with extensive tumor burdens. All 3 CR continue to respond after 28+ to 30+ months. With a median follow-up time of 26 months, the median overall survival duration for all patients is 18.0 months (95% confidence interval 12–24 months). Response was observed to correlate significantly with the IL-2 dose intensity. A dose intensity below 1440 mIU m⁻² year⁻¹ and at least 1440 mIU m⁻²year⁻¹ correlated highly with failure to achieve CR and the successful achieving of CR respectively (P < 0.01). An analysis of the present study database in the context of five previous similar trials demonstrated a significant correlation between IL-2 dose intensity and response rate by regression analysis (r ² = 0.89; P < 0.019). Finally, all toxicities were reversible once the dosing had concluded. Conclusions: IL-2 dose intensity appears to represent a significant determinant of successful clinical outcomes. This dose-intensive approach led to a high proportion of durable responses. Further evaluation of this regimen is warranted. Received: 25 September 1998 / Accepted: 13 November 1998     

Order of patient entry influences outcome for metastatic renal cell cancer after non-myeloablative allogeneic stem cell transplantation

Allogeneic transplantation for renal cell carcinoma has shown encouraging preliminary results. We reviewed the published literature to evaluate the impact of patient selection. Most studies did not include information on prognostic factors. We used patient entry rank within individual studies as a novel surrogate for patient selection, motivated by our own experience of an apparent impact of entry rank. One hundred patients were identified from nine studies. Twenty-six per cent of patients demonstrated either a partial or complete response. Median overall survival was 12.3 months. Grade 2-4 acute graft-versus-host disease correlated with an increased likelihood of response (odds ratio: 5.4, 95% confidence interval: 1.6-18.1, P = 0.006) but not survival. Earlier patient entry rank on each trial was associated with a higher probability of response (P = 0.004) and superior survival (P = 0.004). Patient entry rank served as a powerful prognostic factor, suggesting bias in patient selection that evolved over the course of the study. Further studies are warranted to determine the influence of order of patient entry in other early clinical trial settings.     

Recombinant interferon alfa 2b therapy in a patient with metastatic hepatocellular carcinoma

At present, there is no effective treatment of metastatic hepatocellular carcinoma (HCC). Systemic interferon alfa (IFN-alpha) was found to be of some use in patients with inoperable HCC in two randomized trials. We report a case in which metastatic HCC was cured by systemic IFN-alpha 2b in combination with surgery. A patient developed two bilateral pulmonary metastatic HCC nodules 5 months after the resection of the primary HCC. He was treated with systemic IFN-alpha 2b. One lesion completely disappeared. The other lesion showed an initial response but became resistant to the IFN-alpha 2b therapy after reduction in dosage because of the side effects. This was resected in view of the absence of new metastases after 9 months of IFN-alpha 2b therapy. He remained free from recurrence at 59 months of follow-up. A rare, but reversible, complication of retinal cotton wool spots caused by IFN-alpha 2b occurred in this patient. IFN-alpha 2b is partially effective in treating metastatic HCC. The time for its administration can also serve as an observation period, which is vital in deciding whether definitive surgical treatment of any residual lesions is indicated.     

Delayed hemolytic transfusion reaction due to anti-S antibody in patient with anti-Jk<Superscript>a</Superscript> autoantibody and multiple alloantibodies

We describe the case of a 60-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of an ulcerative colitis, blood transfusion because of rectal bleeding, and surgical removal of descendent and sigmoid colon. At admission, laboratory data showed Hb 6.3 g/dL, reticulocytes 120×10⁹/L, serum total bilirubin 1.2 mg/dL (direct bilirubin: 0.2 mg/dL). Pretransfusion antibody screening procedures were positive. A monospecific autoanti-Jk^a and three alloantibodies (anti-c, -E, -K) were identified by immunohematologic studies. The patient received two units of crossmatch compatible concentrated red blood cells. Six days later biochemical serum values showed Hb 6.2 g/dL, LDH 975 I.U./L and total bilirubin 2.95 mg/dL (direct 0.35 mg/dL). Crossmatches with red cell suspension of transfused blood units and a post-transfusion serum were repeatedly positive. Laboratory tests showed the presence of anti-S alloantobody in the serum and eluate. Moreover, pre-transfusion serum of the patient was retrospectively retested: anti-S was not detected. These data suggested a DHTR. The present case is unusual and interesting because of the association of a rare autoanti-Jk^a, non responsible for anemia, and four alloantibodies of which anti-S involved in a DHTR.     

Chemoimmunotherapy with low dose vinorelbine and interleukin-2 in treatment of patients with metastatic renal cell carcinoma

Systemic therapies employed in patients with metastatic renal cell carcinoma (MRCC) include chemotherapy to immunomodulatory cytokines (interleukin 2 [IL-2], interferon alpha [INFalpha]), chemoimmunotherapy, adoptive immune therapy and anti-angiogenic therapy. Despite this range of treatment alternatives, the optimal therapy for MRCC patients is far from being established. Thus, attempts with novel therapeutic approaches implementing new drug combinations are justified. We conducted a phase II evaluation of a combination of vinorelbine and IL-2, both at low doses, in 30 patients with MRCC. The rationale of the combination was to damage the tumor tissue to the extent necessary to make it more immunogenic while, at the same time, to obtain an efficient immune response through the concomitant administration of IL-2. The treatment, given in different dose combinations and administration times, resulted feasible, with no renal, neurological or hematological toxicity. The overall survival of the whole group of patients is higher than that usually observed following treatment with immunotherapies (18.2 versus 13.3 months, respectively). While the limited number of treated patients does not allow advancing conclusions on the effective activity of the adopted protocol, the results observed are encouraging.     

Digital ischemic necrosis caused by pegylated interferon in a patient with hepatitis C

Pegylated interferon plus ribavirin remains the firstline treatment for patients with hepatitis C virus(HCV) . Interferonαhas the most extensive clinical application and is used for the treatment of chronic hepatitis B virus and hepatitis D virus as well as acute and chronic HCV infections.The attachment of polyethylene glycol to interferon increases its half-life by reducing the rate of absorption after injection,reducing renal and cellular clearance and also decreasing immunogenicity.In this case report,we have described a patient with chronic hepatitis C who developed ischemic necrosis of her fingertips after completing her third course of pegylated interferon and ribavirin.The patient underwent a very extensive workup in order to determine the underlying cause of her digital ischemia which was finally determined to be secondary to the use of pegylated interferon.