Successful Pregnancy Outcomes in Paroxysmal Nocturnal Hemoglobinuria with Long-Term Eculizumab Treatment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4576-4576 ◽  
Author(s):  
Richard Kelly ◽  
Louise Arnold ◽  
Stephen J. Richards ◽  
Anita Hill ◽  
Charlotte Bomken ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Abdominal Pain ◽  
Breast Milk ◽  
Cord Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Post Partum ◽  
Serum Levels ◽  
Complement Inhibitor ◽  
Terminal Complement

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a lack of the terminal complement inhibitor CD59 on erythrocytes that renders these cells susceptible to chronic hemolysis resulting in anemia, fatigue, abdominal pain, kidney dysfunction, pulmonary hypertension, and life-threatening thromboembolism (TE). During pregnancy, hemolysis frequently worsens and the incidence of TE increases, posing a high risk of both fetal and maternal mortality. Eculizumab is a terminal complement inhibitor that reduces hemolysis, transfusion requirements, and TE while improving fatigue and quality of life in patients with PNH. Eculizumab contains a hybrid constant region with components of both IgG2 and IgG4. Whether eculizumab crosses the placenta is not known. The eculizumab clinical trial protocols specified withdrawal of patients who became pregnant during the study. There were 5 reported pregnancies during the PNH clinical trials (n=195) prior to withdrawal from the study. To evaluate the safety and efficacy of eculizumab in the management of PNH during pregnancy, we reviewed the physician-reported adverse events (AEs), PK/PD, and distribution of eculizumab, duration of drug exposure during gestation, complications during and after pregnancy, and general health of the newborn in patients with PNH who became pregnant during the eculizumab clinical trials. Of the 5 reported pregnancies, one patient elected termination and 3 patients withdrew from eculizumab therapy between 4 to 16 weeks of gestation and continued pregnancy through term. There were no apparent complications or AEs related to drug and all 3 patients delivered healthy newborns. One patient was treated with low molecular weight heparin (LMWH) from the time she discontinued eculizumab to three months after delivery. She developed hyperpyrexia and was diagnosed with fever of unknown origin shortly after delivery. She was treated and then discharged. There have been no reported postpartum complications in any of these deliveries to date. The fifth patient withdrew from the study but continued on eculizumab treatment throughout the whole pregnancy and post-partum. She initiated eculizumab treatment in 2002 reducing her LDH from 10,300U/L to 490 U/L (normal range 150 to 480 U/L). Her transfusion requirement reduced from 4 units every 6 weeks to 2 units per year in order to maintain her hemoglobin above 8 g/dl. She was commenced on LMWH at week 8 of gestation and she remained on it for the duration of her pregnancy and postpartum. During pregnancy, she was transfused more frequently to maintain her hemoglobin above 9 g/dl. At week 28 of gestation, she experienced an episode of hemoglobinuria and abdominal pain for 3–4 days prior to her next dose of eculizumab and therefore the dosing interval was adjusted from 14 to 12 days (11 days to avoid weekends) as per the approved 900mg dose. She had no further episodes of breakthrough and her LDH levels were maintained below 450 U/L. The patient was induced at term and delivered a healthy newborn. On the day of delivery, there was no detectable eculizumab in the cord blood (see table). At day 1 and 9 postpartum, there was no detectable eculizumab in breast milk samples. To date, the patient shows no clinical signs of thrombosis or other morbidities typically associated with PNH. The first evaluation of eculizumab treatment from conception to delivery in a patient with PNH treated with eculizumab demonstrated that the drug was tolerated and the pregnancy was successful. There was no evidence of thromboses or other morbidities during the postpartum period. There have been no reported events of congenital anomaly/birth defects in the offspring of any patient with PNH who became pregnant during participation in our clinical studies. Further, there are currently two patients being followed who received eculizumab treatment either during the last trimester (started eculizumab at week 26) or throughout gestation to term. Pregnancy in PNH is associated with an extremely high maternal risk. A review of the 5 clinical trial cases demonstrated that patients receiving eculizumab during pregnancy had no obvious complications through the post-partum period and that a slightly higher dose of eculizumab may be required during pregnancy than in non-pregnant patients with PNH. In addition, eculizumab does not appear to cross the placenta or to be secreted into breast milk. Eculizumab therapy may play a significant role in the management of pregnancy in patients with PNH. Table. Eculizumab levels at delivery Eculizumab Levels (μg/ml)* Post Partum Day 0 Day1 Day 9** NM. Not Measured *, a level of 35 μg/ml or more has been shown to completely block terminal complement activation **An additional dose was given between Day 1 and Day 9 Eculizumab serum levels in mother 116.1 81.3 146 Eculizumab serum levels in cord blood 0 NM NM Eculizumab in breast milk 0 0 0

Safety and Efficacy of the Terminal Complement Inhibitor Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Interim Shepherd Phase III Clinical Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 971-971 ◽  
Author(s):  
Neal S. Young ◽  
Elisabetta Antonioli ◽  
Bruno Rotoli ◽  
Hubert Schrezenmeier ◽  
Jörg Schubert ◽  
...  
Keyword(s):  
Clinical Study ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Phase Iii ◽  
Complement Inhibitor ◽  
Intravascular Hemolysis ◽  
Safety And Efficacy ◽  
Transfusion Requirements ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Terminal Complement

Abstract In paroxysmal nocturnal hemoglobinuria (PNH), lack of the GPI-anchored terminal complement inhibitor CD59 from blood cells renders erythrocytes susceptible to chronic hemolysis resulting in anemia, fatigue, thrombosis, poor quality of life (QoL), and a dependency on transfusions. Eculizumab, a terminal complement inhibitor, reduced intravascular hemolysis and transfusion requirements in transfusion dependent patients with normal or near-normal platelet counts in a randomized placebo-controlled trial (TRIUMPH). SHEPHERD, an open-label, non-placebo controlled 52-week phase III clinical study, is underway to evaluate the safety and efficacy of eculizumab in a broader PNH population including patients with significant thrombocytopenia and/or lower transfusion requirements. Eculizumab was dosed as follows: 600 mg IV every 7 days x 4; 900 mg 7 days later; and then 900 mg every 14±2 days. Eculizumab was administered to 97 patients at 33 international sites. In a pre-specified 6-month interim analysis, the most frequent adverse events were headache (50%), nasopharyngitis (23%), and nausea (16%); most were mild to moderate in severity. No infections or serious adverse events were reported as “probably” or “definitely” related to drug. Intravascular hemolysis, the central clinical manifestation in PNH and the primary surrogate efficacy endpoint of the trial, was significantly reduced in eculizumab patients as assessed by change in lactate dehydrogenase (LDH) area under the curve (p<0.001). LDH levels decreased from a median of 2,051 U/L at baseline to 270 U/L at 26 weeks (p<0.001; normal range 103–223 U/L). Control of intravascular hemolysis resulted in an improvement in anemia as transfusion requirements decreased from a median of 4.0 PRBC units/patient pre-treatment to 0.0 during treatment (p<0.001), approximately 50% of the patients were rendered transfusion independent (P<0.001), and hemoglobin levels increased (p<0.001). Fatigue, as measured by both the FACIT-Fatigue and EORTC QLQ-C30 instruments, was significantly improved with eculizumab treatment as compared to baseline (p<0.001 for each). Other EORTC-QLQ-C30 patient reported outcomes demonstrating improvement included global health status (p<0.001), all 5 patient functioning subscales (p<0.001) and 7 of 9 symptom/single item subscales (p≤0.03). These results demonstrate that the beneficial effects of eculizumab in PNH are applicable to a much broader patient population than previously studied and further underscore that eculizumab treatment markedly reduces intravascular hemolysis, thereby providing clinical benefit to treated patients. The trial will complete in September 2006 and the final results from this 52-week study will be presented.

scholarly journals Recurrent and Progressive Abdominal Pain and Enteritis in a Japanese Patient with Paroxysmal Nocturnal Hemoglobinuria

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Akihisa Hino ◽  
Yukiko Yamashita ◽  
Mitsuhiro Yamaguchi ◽  
Yasuhiko Azenishi
Keyword(s):  
Abdominal Pain ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Japanese Patient ◽  
Treatment Initiation ◽  
Young Male ◽  
Recurrent Abdominal Pain ◽  
Complement Inhibitor ◽  
Clinical Investigations ◽  
Lactate Dehydrogenase C ◽  
D Dimer

This case report describes a young male patient with recurrent abdominal pain persisting for more than 16 months. Clinical investigations showed signs of inflammation and pancytopenia. A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was made 9 months after the onset of the abdominal pain, following endoscopic examinations that revealed evidence of a previously unknown hemorrhage. Regular monitoring indicated that the abdominal pain was associated with elevations in lactate dehydrogenase, C-reactive proteins, and D-dimer levels. The patient started treatment with the complement inhibitor eculizumab shortly after it was approved for use in Japanese PNH patients with hemolysis. Resolution of the abdominal pain and normalization of clinical parameters were noted within 3 weeks from treatment initiation.

Disopyramide and N-Monodesalkyl Disopyramide in Serum and Breast Milk

DICP ◽  
1989 ◽  
Vol 23 (1) ◽  
pp. 56-57 ◽  
Author(s):  
Allan J. Ellsworth ◽  
John R. Horn ◽  
Vidmantas A. Raisys ◽  
Lea Ann Miyagawa ◽  
Judy L. Bell
Keyword(s):  
Drug Therapy ◽  
Breast Milk ◽  
Cord Blood ◽  
Serum Levels ◽  
Maternal Serum ◽  
Serum Concentrations ◽  
Drug Concentrations ◽  
Serum And Urine

Maternal serum and breast milk were obtained to determine the concentration of disopyramide (DP) and its metabolite N-monodesalkyl disopyramide (NMD) from a woman requiring antidysrhythmic drug therapy. Infant serum and urine were also obtained for drug concentrations. DP 450 mg tid resulted in peak maternal serum concentrations of 4.0 μg/mL and 2.2 μg/mL for DP and NMD, respectively. Breast milk concentrations averaged 1.06 and 6.24 times the serum levels for DP and NMD, respectively. No DP was measurable in the infant's serum except for cord blood, which contained 0.7 μg/mL DP, 26 percent of simultaneous maternal concentration, and 0.9 μg/mL NMD, which represented 43 percent of the maternal concentration. Infant urine collected over an eight-hour period contained 3.3 μg/mL of DP and 3.7 μg/mL of NMD.

Treatment with the Terminal Complement Inhibitor Eculizumab Improves Anemia in Patients with Paroxysmal Nocturnal Hemoglobinuria: Phase III Triumph Study Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 124-124 ◽  
Author(s):  
Jörg Schubert ◽  
Peter Hillmen ◽  
Ulrich Dührsen ◽  
Neal S. Young ◽  
Modupe Elebute ◽  
...  
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Statistical Significance ◽  
Phase Iii ◽  
Effective Control ◽  
Complement Inhibitor ◽  
Intravascular Hemolysis ◽  
Transfusion Independence ◽  
Transfusion Requirements ◽  
Study Results ◽  
Terminal Complement

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a potentially life-threatening acquired hemolytic anemia in which red blood cells (RBCs) lacking complement inhibitory proteins are sensitive to complement-mediated destruction or hemolysis. Intravascular hemolysis in these patients often results in the need for clinical support with packed RBCs (PRBCs) in order to maintain tolerable hemoglobin levels. Eculizumab, a terminal complement inhibitor, has recently been shown in a placebo-controlled randomized phase III clinical trial (TRIUMPH) to reduce intravascular hemolysis and transfusion requirements in patients with PNH. Reported here is a detailed analysis of the effect of eculizumab on various parameters of anemia in these study patients. Eculizumab-treated patients, as compared to placebo, showed an 85.8% decrease in intravascular hemolysis (as measured by LDH area under the curve, p<0.001). This reduction in hemolysis with eculizumab resulted in a 2.5-fold increase in PNH RBC mass from a median of 0.81x1012 cells/L at baseline to 2.05x1012 cells/L at 26 weeks (p<0.001), while the PNH RBC mass in placebo-treated patients remained relatively unchanged (from a median of 1.09x1012 cells/L to 1.16x1012 cells/L). The increase in PNH RBC mass was associated with an increase in hemoglobin levels in eculizumab-treated patients relative to placebo (p<0.001). The number of PRBC units transfused decreased from a median of 10.0/patient with placebo to 0.0/patient with eculizumab (p<0.001), and 51.2% of eculizumab-treated patients became transfusion independent (versus 0.0% of placebo patients, p<0.001). Even patients who required some transfusions while on eculizumab showed a marked reduction in transfusion requirement from a median of 10.0 units per patient with placebo to 6.0 units/patient with eculizumab (p<0.001). The reduction in PRBC units transfused with eculizumab was observed regardless of transfusion requirements prior to treatment, with statistical significance reached in 3 of 3 pre-treatment transfusion strata (4 to 14 units/year; 15–25 units/year; and >25 units/year, p<0.001 for each stratum). Significant reductions were observed in intravascular hemolysis (LDH) in eculizumab-treated patients that achieved transfusion independence (p<0.001) as well as those that did not (p<0.001). Taken together, these data demonstrate that effective control of intravascular hemolysis in PNH with eculizumab results in a substantial improvement in anemia, as evidenced by an increase in endogenous RBC mass, an improvement in hemoglobin levels, and a reduction in transfusion requirements. Substantial and significant reductions in intravascular hemolysis and improvements in anemia with eculizumab are demonstrated regardless of historical transfusion requirements or whether patients achieve transfusion independence during treatment.

Safety and Efficacy of the Terminal Complement Inhibitor Eculizumab in Japanese Patients with Paroxysmal Nocturnal Hemoglobinuria: AEGIS Phase II Clinical Study Results.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3438-3438 ◽  
Author(s):  
Yuzuru Kanakura ◽  
Kazuma Ohyashiki ◽  
Tsutomu Shichishima ◽  
Shinichiro Okamoto ◽  
Kiyoshi Ando ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Japanese Patients ◽  
Phase Iii ◽  
Complement Inhibitor ◽  
Intravascular Hemolysis ◽  
Safety And Efficacy ◽  
Transfusion Requirements ◽  
Terminal Complement

Abstract In patients with paroxysmal nocturnal hemoglobinuria (PNH), lack of the GPI-anchored terminal complement inhibitor CD59 on hematopoietic stem cells and subsequently matured blood cells results in chronic intravascular hemolysis and thrombosis. The patients also show kidney disease and pulmonary hypertension in addition to disabling fatigue, abdominal pain and impaired quality of life. Eculizumab is a humanized MoAb against a terminal complement molecule C5, and has been evaluated in 2 phase III studies in North America, Western Europe and Australia. Eculizumab significantly reduced hemolysis, anemia, transfusion requirements, and thrombotic events, and improved fatigue, renal impairment and quality of life. We conducted an open-label single-arm phase II study (AEGIS) to evaluate the safety and efficacy of eculizumab in Japanese patients with PNH relative to the two phase III eculizumab studies previously reported. The AEGIS study criteria included patients with significant thrombocytopenia (platelet counts ≥ 30x109/L) and/or minimal transfusion requirements (1 or more transfusion episodes in the preceding 2 years). Eculizumab was dosed as follows: 600mg weekly for 4 weeks; 900mg one week later; and then 900mg every other week for a total of 12 weeks of therapy. Patients received meningococcal vaccine 2 weeks prior to treatment. Eculizumab was administered to 29 Japanese patients at 9 institutions. The median patient age was 47 years (range 26–70 years), median platelet count was 150x109/L (range 28–291x109/L), 45% had a history of aplastic anemia or MDS, and 48% were taking corticosteroids. Eculizumab serum levels were sufficient to completely block complement. Twenty seven out of 29 patients completed the study. Intravascular hemolysis, the primary efficacy endpoint of the trial, was rapidly and significantly reduced with eculizumab treatment. Lactate dehydrogenase (LDH) decreased 86% from a median of 1,814 U/L at baseline to a median of 244 U/L at 12 weeks of treatment (P<0.001; normal range 103–223 U/L). Control of hemolysis resulted in improvement in anemia; hemoglobin levels increased from baseline (p=0.002 respectively). Transfusion requirements decreased 71% from a mean (SE) of 5.2 (±1.04) PRBC units/patient during the 12-week pre-treatment period to 1.5 (±0.67) units/patient during 12 weeks of eculizumab treatment (P<0.001 for the prespecified median change). Transfusion independence was achieved in 67% (14/21) of patients who were transfusion-dependent prior to treatment (P<0.001). Fatigue levels, as measured by the FACIT-Fatigue instrument, significantly improved within one week of eculizumab treatment, with a median increase of 5.0 points at 12 weeks (P<0.001). A change of 3 or more points is considered clinically meaningful. A post hoc analysis was performed to evaluate the effect of eculizumab on chronic kidney disease (CKD), measured as an improvement or worsening in CKD stage during treatment according to the KDOQI CKD published guidelines. Eculizumab improved CKD in 41% (12/29) of patients, while 55% (16/29) maintained stable kidney function, and only 3.4% (1/29) showed worsening (P<0.001). There were five reported thrombotic events in patients prior to eculizumab and no reported events in treated patients to-date. The drug was safe and well tolerated in all patients. The most frequent adverse events (AEs) were headache (52%), nasopharyngitis (41%), and nausea (21%). Most AEs were mild to moderate in severity and not considered related to eculizumab. No serious AEs were reported as probably related to drug. In summary, this trial demonstrates that eculizumab is safe and well tolerated in Japanese patients with PNH and provides beneficial effects in PNH similar to those observed in previous phase III trials. Table 1: Efficacy of Eculizumab Baseline 12 weeks Treatment Change From Baseline P-Valuea aOverall mixed model analysis bBaseline represents the number of units transfused during the 12 week period prior to treatment. One PRBC unit is prepared from 200 ml of donor peripheral blood. cA change of ≥ 3 is considered clinically meaningful LDH, U, L Median (mean ± SE) 1,814 (1,845 ±115) 244 (399 ± 99) P < 0.001 Transfusions (PRBC Units/Patient)bmedian (mean ± SE) 2.0 (5.2 ±1.04) 0.0 (1.5 ± 0.67) P < 0.001 Hemoglobin (g/dL) Median (mean ± SE) 7.5 (7.3±0.3) 9.0 (8.9 ± 0.4) P =0.002 FACIT-fatigue scorec Median (mean ± SE) 41.0 (38.5 ±1.9) 43.0 (42.6± 1.5) +5.0 (4.1 ±2.3) P < 0.001

Effect of Reducing Intravascular Hemolysis on Ferritin Homeostasis in Eculizumab Treated Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3437-3437
Author(s):  
Alexander Roeth ◽  
Joerg Schubert ◽  
Christina Hock ◽  
Sandra Christoph ◽  
Ulrich Duehrsen
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Phase Iii ◽  
Thromboembolic Events ◽  
Complement Inhibitor ◽  
Intravascular Hemolysis ◽  
Normal Range ◽  
Iron Depletion ◽  
Transfusion Requirements ◽  
Iron Parameters ◽  
Terminal Complement

Abstract BACKGROUND: In paroxysmal nocturnal hemoglobinuria (PNH), the lack of the GPI-anchored terminal complement inhibitor CD59 on erythrocytes renders these cells susceptible to continuous complement mediated hemolysis. Hemolysis leads to anemia, fatigue, red blood cell transfusions, renal impairment and increases the risk of thromboembolic events. Urinary iron loss is also common in patients with PNH due to intravascular hemolysis. Eculizumab is a terminal complement inhibitor that has been evaluated in two phase III studies. In previous studies eculizumab significantly reduced intravascular hemolysis (characterized by significant reduction of LDH levels) and significantly reduced transfusion requirements as well as thromboembolic events. In this study we evaluated the change in hemolytic parameters and levels of ferritin parameters in PNH patients treated with eculizumab in two centers (Essen and Homburg/Saar). METHODS: Nineteen PNH patients were treated with eculizumab as follows: 4 x 600mg IV every 7±2 days; 900 mg 7±2 days later; and then 900 mg every 14±2 days. The median therapy duration was 31 months (range 1–40 months). Hemolysis, transfusion requirements and serum iron parameters were analyzed over time of treatment. RESULTS: Eculizumab effectively inhibited intravascular hemolysis in all PNH patients as evidenced by an 79% decrease in LDH levels (mean±SD: 2,110±802 to 349±182 U/l (normal range: 100–247); p=0.0001) and reduced transfusion requirements. Persistent elevation of reticulocytes as well as the reduction of haptoglobin and hemopexin were observed in most patients, which suggest continuing extravascular hemolysis. Interestingly, we observed an 709% increase in ferritin levels in patients treated with eculizumab (median from 73 to 965 μg/l (normal range: 20–290 μg/L); p=0.001). This was more pronounced in patients still requiring some transfusions. Three patients were started on oral iron depletion therapy. No thromboembolic or serious adverse events were observed in eculizumab-treated patients. Two PNH patients were diagnosed with PNH-associated hematological disease (MDS, myelofibrosis). SUMMARY/CONCLUSIONS: Eculizumab is safe and well tolerated in the analyzed cohort of PNH patients. Iron parameters in PNH patients treated with eculizumab should be monitored to determine if iron supplementation should be altered or iron depletion therapy should be considered. While some extravascular hemolysis may persist, intravascular hemolysis is effectively controlled with eculizumab and is associated with a concomitant improvement in anemia and quality of life.

Eculizumab Treatment of Paroxysmal Nocturnal Hemoglobinuria Relapsing After Bone Marrow Transplant and Subsequent Clonal: Case Report

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5274-5274
Author(s):  
Andres L. Brodsky ◽  
Brenner Sabando Velez ◽  
Curutchet Ragusin
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Abdominal Pain ◽  
Case Report ◽  
Hematopoietic Stem Cell ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Clone Size ◽  
Hematopoietic Stem ◽  
Chronic Hemolysis ◽  
Terminal Complement

Abstract Abstract 5274 Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic and life-threatening hematopoietic stem cell disorder characterized by deficiency of the GPI-anchored complement inhibitory proteins CD55 and CD59 on blood cells. The resulting uncontrolled complement activation is responsible for chronic hemolysis and can lead to serious clinical morbidities including thromboembolism (TE) and chronic kidney disease (CKD), which have been shown to increase risk of mortality. Patients may also experience debilitating quality-of-life (QoL) issues, including fatigue, shortness of breath, erectile dysfunction, and abdominal pain, attributed to chronic hemolysis and resultant nitric oxide scavenging by free hemoglobin. Although hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for PNH, the risk for substantial morbidities and mortality still exist. In patients with PNH undergoing HSCT, up to 45% die or develop acute or chronic graft-versus-host disease. Eculizumab, a first-in-class terminal complement inhibitor, is the only approved treatment for patients with PNH. By inhibiting terminal complement activity and chronic hemolysis, eculizumab reduces the incidence of TE, CKD, and transfusion requirements, improves anemia and QoL, and normalizes survival in patients with PNH. Aim: Report the benefits of eculizumab in a patient with PNH who relapsed after HSCT. Case Report: A 27-year-old woman presented in December 1993 with fever, diarrhea, hemoglobinuria, and acute renal failure requiring temporary hemodialysis (Table). She was subsequently diagnosed with PNH. In February 1995, allogeneic HSCT from an HLA-identical sibling donor was performed. In 2003, 8 years after successful engraftment, the patient relapsed and presented with hemoglobinuria, abdominal pain, corticosteroid dependence requiring 20 to 40 mg methylprednisone, and high transfusional requirements. In November 2007, she had a granulocyte clone size of 37.2% as determined by flow cytometry. In June 2009, she started eculizumab therapy which was associated with a rapid reduction in lactate dehydrogenase (LDH) from 4964U/L to 456U/L. She subsequently achieved resolution of asthenia, disabling fatigue, and abdominal pain, as well as transfusion independence and improvement in hemoglobin. In May 2010, she had a granulocyte clone size of 86.1% as determined by both CD55- and CD59-negative cells, and a granulocyte clone size of 98.7% as determined by CD16b-negative cells. Conclusions: The only potential cure for PNH—bone marrow transplantation—is associated with high risks of morbidity and mortality; therefore, for most patients the associated risks preclude this option. In this case study, we show that HSCT may not be curative in all patients and the PNH associated symptoms can arise after BMT. The potential benefits of eculizumab in this patient population should be considered in light of recent data that demonstrated normalized survival in PNH patients receiving long-term eculizumab treatment. Disclosures: Brodsky: Alexion Pharmaceuticals, Inc.: Consultancy, Speakers Bureau. Velez:Alexion Pharmaceuticals, Inc.: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document