Stiffer Spleen Predicts Higher Bone Marrow Fibrosis and Higher JAK2 Allele Burden in Patients With Myeloproliferative Neoplasms

A total of 63 myeloproliferative neoplasms [MPN; 9 polycythemia vera (PV), 32 essential thrombocythemia (ET), and 22 myelofibrosis (MF)] underwent spleen stiffness (SS) measurement by vibration-controlled transient elastography equipped with a novel spleen-dedicated module. Higher SS values significantly correlated with grade 2-3 bone marrow (BM) fibrosis (p=0.035), with hemoglobin level <10 g/dl (p=0.014) and with white blood cells ≥10,000/μl (p=0.008). Median SS was significantly higher in MF patients compared to ET and PV (p=0.015). SS also correlated with higher JAK2 variant allele frequency (p=0.02). This study identifies SS as a potential noninvasive tool that reflects BM fibrosis and the mutational burden in MPN.

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Spleen Stiffness Measurement By Transient Elastography As a Predictor of Bone Marrow Fibrosis in Primary Myelofibrosis Patients

Blood ◽

10.1182/blood.v124.21.1825.1825 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1825-1825

Author(s):

Alessandra Iurlo ◽

Daniele Cattaneo ◽

Mariangela Giunta ◽

Umberto Gianelli ◽

Giovanni Casazza ◽

...

Keyword(s):

Bone Marrow ◽

Portal Hypertension ◽

Liver Disease ◽

Transient Elastography ◽

Liver Stiffness ◽

Primary Myelofibrosis ◽

Bone Marrow Fibrosis ◽

Predicted Probability ◽

Spleen Stiffness ◽

Marrow Fibrosis

Abstract Introduction: transient elastography (TE) is a standardized, non-invasive tool which predicts severity of chronic liver disease (CLD). Owing to the known relationships between liver fibrosis, portal hypertension and splenomegaly, the measurement of spleen stiffness (SS) has been evaluated as an alternative and/or complementary method to liver stiffness (LS) in order to evaluate liver disease severity. In particular, a significant correlation between SS and portal hypertension has been established with hemodynamic measurements, demonstrating that SS accurately predicts the risk of both esophageal varices and clinical decompensation in patients with viral cirrhosis. Recently, we conducted a study in CLD patients with the aim to assess the diagnostic accuracy of combined LS and SS in the prediction of liver fibrosis and portal hypertension; it also included 64 healthy volunteers and 48 patients with a previous diagnosis of hematological malignancies as control population. Among the few hematological patients enrolled in that study, a significant correlation between SS and bone marrow fibrosis grade (p<0.01) was found and it was more pronounced in the 23 primary myelofibrosis (PMF) patients than in those with other hematological neoplasms. Methods: to validate further these preliminary observations, we enrolled 108 patients with a clinical and histological diagnosis of PMF based on WHO 2008 criteria. All patients concurrently underwent liver and spleen TE, in conjunction with a bone marrow biopsy, ultrasound evaluation of spleen size and chemistries. Once we found normal LS values granted for the absence of liver disease potentially interfering with SS assessments, according to the updated WHO classification, we considered only two main bone marrow fibrosis categories defined as follows: pre-fibrotic/early fibrotic (MF-0/1) and advanced fibrotic stage (MF-2/3). Results: transient elastography of the liver and spleen was successfully performed in 88 PMF patients (81.5%), whereas 20 (18.5%) had indeterminate spleen-TE results; however, this rate of spleen-TE failure is similar to that reported by previous studies in CLD patients (15 to 20% of all cases). The median liver-TE and spleen-TE values were 7.1 kPa (range 3.5-19.6) and 40.1 kPa (range 11.8–75.0), respectively. In a univariate analysis both spleen (p<.0001) and liver stiffness (p=.0074) correlated with the severity of bone marrow fibrosis, whereas age, gender and the PMF prognostic scoring systems IPSS, DIPSS and DIPSS-plus did not. Furthermore, bone marrow fibrosis did not correlate with the presence of JAK2 V617F or CALR mutations, whereas it did with Hb (p=0.0001), LDH (p<.0001) and peripheral blood CD34-positive cells count (p=0.0003). At multivariate analysis, only SS, LDH and CD34-positive cells count maintained a significant correlation with bone marrow fibrosis, with a discriminative ability assessed by the c statistic of 0.904 (95% CI, 0.841-0.967). According to these results, we were able to propose an equation for the estimation of the probability of being MF-2/3, arranged as follows: probability MF-2/3= exp[-4.83+0.0380*SS+0.0039*LDH+0.0148*CD34]/[1+exp(-4.83+0.0380*SS+0.0039*LDH+0.0148*CD34)]. The model entails two decisional threshold values that predict the probability of diagnosing PMF severity: the best cut-off for the diagnosis of MF-0/1 was 0.15 (negative predictive value=0.97) and the best cut-off for the diagnosis of MF-2/3 was 0.73 (positive predictive value=0.94), with an accuracy of 97% for the former and 94% for the latter. Figure 1 describes the two decisional thresholds and the distribution of our patients in the MF-0/1 and MF-2/3 categories. Conclusions: to our knowledge, this study represents the first attempt to evaluate the entity of SS in PMF patients as a measure of disease severity. Furthermore, our results allow us to suggest the use of SS as a surrogate marker of bone marrow fibrosis, particularly following the fibrogenetic progression of the disease, especially when it is considered together with such routine chemistries as LDH and CD34-positive cells count, a finding that may limit the need for an invasive and more expensive procedure like bone marrow biopsy in the management of PMF patients. Figure 1 Patients’ distribution in the two main bone marrow fibrosis categories according to the predicted probability cut-off values Figure 1. Patients’ distribution in the two main bone marrow fibrosis categories according to the predicted probability cut-off values Disclosures No relevant conflicts of interest to declare.

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Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181025091128 ◽

2019 ◽

Vol 18 (14) ◽

pp. 1936-1951 ◽

Cited By ~ 5

Author(s):

Raghav Dogra ◽

Rohit Bhatia ◽

Ravi Shankar ◽

Parveen Bansal ◽

Ravindra K. Rawal

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Overall Survival ◽

Acute Myeloid Leukemia ◽

Adverse Effects ◽

Blood Cells ◽

Myeloid Leukemia ◽

White Blood Cells ◽

Phase Iii ◽

Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽

10.1182/blood.v90.6.2148 ◽

1997 ◽

Vol 90 (6) ◽

pp. 2148-2159 ◽

Cited By ~ 118

Author(s):

Harshal H. Nandurkar ◽

Lorraine Robb ◽

David Tarlinton ◽

Louise Barnett ◽

Frank Köntgen ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Blood Cells ◽

Bone Marrow Cells ◽

White Blood Cells ◽

Null Mutation ◽

Wild Type ◽

Normal Numbers ◽

Interleukin 11 ◽

Marrow Cells

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

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The Prevalence of Myeloproliferative Disorders in A Group of Iraqi Patients And Its Relation To Blood Indices Parameters

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5284 ◽

2020 ◽

Vol 8 (A) ◽

pp. 660-665

Author(s):

Marwa Abdulnabi ◽

Enass Abdul Kareem Dagher Al-Saadi

Keyword(s):

Bone Marrow ◽

Blood Cells ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Disorders ◽

Myelogenous Leukemia ◽

High Exposure ◽

Female Ratio ◽

Blood Samples ◽

Blood Indices ◽

Male To Female

AIM: The aim of this study was to measure the prevalence of myeloproliferative disorders in a sample of Iraqi patients and to measure the changes in patients’ blood parameters. BACKGROUND: Myeloproliferative disorders are a group of neoplasms affecting the bone marrow progenitor cells characterized by excess cells with a risk of transforming to acute leukemia. There is a gap in knowledge about the prevalence of Iraqi population. Thus, we investigated the prevalence and distribution of different types of myeloproliferative disorders in a sample of Iraqi patients. MATERIALS AND METHODS: Cross-sectional study is done at the National Center of Hematology from November 2019 till March 2020 on 75 patients who were diagnosed by a specialist hematopathologist to have one subtype of myeloproliferative disorders (MPDs). Blood samples were taken from them and analyzed to get complete blood count, blood film, bone marrow aspirate, and biopsy that were analyzed for each patient. Blood samples were taken from them and analyzed in terms of blood indices, which include red blood cells, white blood cells, and platelets. RESULTS: The 75 patients were found to be comprising 35 chronic myelogenous leukemia (CML) patients (46.7%), myelofibrosis 22 patients (29.3%), essential thrombocythemia (ET) 9 patients (12%), and polycythemia vera (PV) 9 patients (12%). In terms of male/female ratios, they were as follows: Myeloproliferative neoplasms (MPNs) male-to-female ratio is 1.2, CML= 0.94, myelofibrosis= 2.14 and ET= 0.5 and PV male-to-female ratio is 2. CONCLUSIONS : MPN male-to-female ratio in Iraq, which is 1.2, CML is the most common subtype. Regarding myelofibrosis, in our study, the male-to-female ratio is 2.14, which is much higher other countries. This could be attributed to high exposure to benzene and toluene which are well known to be causative agents for myelofibrosis. Regarding ET or PV, the male-to-female ratios were compatible with other countries.

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Segmentation of Leukemia Cells Using Clustering

International Journal of Synthetic Emotions ◽

10.4018/ijse.2019070103 ◽

2019 ◽

Vol 10 (2) ◽

pp. 39-48

Author(s):

Eman Mostafa ◽

Heba A. Tag El-Dien

Keyword(s):

Bone Marrow ◽

Cancer Cells ◽

Blood Cells ◽

White Blood Cells ◽

Leukemia Cells ◽

Microscopic Image ◽

Processing Stage ◽

Clustering Techniques ◽

Fuzzy C Means

Leukemia is a blood cancer which is defined as an irregular augment of undeveloped white blood cells called “blasts.” It develops in the bone marrow, which is responsible for blood cell generation including leukocytes and white blood cells. The early diagnosis of leukemia greatly helps in the treatment. Accordingly, researchers are interested in developing advanced and accurate automated techniques for localizing such abnormal blood cells. Subsequently, image segmentation becomes an important image processing stage for successful feature extraction and classification of leukemia in further stages. It aims to separate cancer cells by segmenting the microscopic image into background and cancer cells that are known as the region of interested (ROI). In this article, the cancer blood cells were segmented using two separated clustering techniques, namely the K-means and Fuzzy-c-means techniques. Then, the results of these techniques were compared to in terms of different segmentation metrics, such as the Dice, Jac, specificity, sensitivity, and accuracy. The results proved that the k-means provided better performance in leukemia blood cells segmentation as it achieved an accuracy of 99.8% compared to 99.6% with the fuzzy c-means.

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Subchronic Oral Toxicity Study of Decitabine in Combination With Tetrahydrouridine in CD-1 Mice

International Journal of Toxicology ◽

10.1177/1091581814524994 ◽

2014 ◽

Vol 33 (2) ◽

pp. 75-85 ◽

Cited By ~ 7

Author(s):

Pramod Terse ◽

Kory Engelke ◽

Kenneth Chan ◽

Yonghua Ling ◽

Douglas Sharpnack ◽

...

Keyword(s):

Bone Marrow ◽

Combination Therapy ◽

Food Consumption ◽

Blood Cells ◽

Recovery Period ◽

White Blood Cells ◽

Clinical Pathology ◽

High Dose ◽

Severe Toxicity ◽

Oral Toxicity

Decitabine (5-aza-2′-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia. A study was conducted in mice to assess safety of this combination therapy using oral gavage of DAC and THU administered 1 hour prior to DAC on 2 consecutive days/week for up to 9 weeks followed by a 28-day recovery to support its clinical trials up to 9-week duration. Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC. Doses were 167 mg/kg THU followed by 0, 0.2, 0.4, or 1.0 mg/kg DAC; THU vehicle followed by 1.0 mg/kg DAC; or vehicle alone. End points evaluated were clinical observations, body weights, food consumption, clinical pathology, gross/histopathology, bone marrow micronuclei, and toxicokinetics. There were no treatment-related effects noticed on body weight, food consumption, serum chemistry, or urinalysis parameters. Dose- and gender-dependent changes in plasma DAC levels were observed with a Cmax within 1 hour. At the 1 mg/kg dose tested, THU increased DAC plasma concentration (∼10-fold) as compared to DAC alone. Severe toxicity occurred in females receiving high-dose 1 mg/kg DAC + THU, requiring treatment discontinuation at week 5. Severity and incidence of microscopic findings increased in a dose-dependent fashion; findings included bone marrow hypocellularity (with corresponding hematologic changes and decreases in white blood cells, red blood cells, hemoglobin, hematocrit, reticulocytes, neutrophils, and lymphocytes), thymic/lymphoid depletion, intestinal epithelial apoptosis, and testicular degeneration. Bone marrow micronucleus analysis confirmed bone marrow cytotoxicity, suppression of erythropoiesis, and genotoxicity. Following the recovery period, a complete or trend toward resolution of these effects was observed. In conclusion, the combination therapy resulted in an increased sensitivity to DAC toxicity correlating with DAC plasma levels, and females are more sensitive compared to their male counterparts.

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Critical requirement for Stat5 in a mouse model of polycythemia vera

Blood ◽

10.1182/blood-2011-03-345215 ◽

2012 ◽

Vol 119 (15) ◽

pp. 3539-3549 ◽

Cited By ~ 77

Author(s):

Dongqing Yan ◽

Robert E. Hutchison ◽

Golam Mohi

Keyword(s):

Polycythemia Vera ◽

Blood Cells ◽

Myeloproliferative Neoplasms ◽

White Blood Cells ◽

Strong Support ◽

Primary Myelofibrosis ◽

Blood Parameters ◽

Critical Function ◽

Critical Requirement ◽

Multiple Signaling

The JAK2V617F mutation has been identified in most cases of Ph-negative myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Expression of JAK2V617F results in constitutive activation of multiple signaling molecules/pathways. However, the key signaling downstream of JAK2V617F required for transformation and induction of MPNs remains elusive. Using a mouse genetic strategy, we show here that Stat5 is absolutely required for the pathogenesis of PV induced by Jak2V617F. Whereas expression of Jak2V617F in mice resulted in all the features of human PV, including an increase in red blood cells, hemoglobin, hematocrit, white blood cells, platelets, and splenomegaly, deletion of Stat5 in the Jak2V617F knockin mice normalized all the blood parameters and the spleen size. Furthermore, deletion of Stat5 completely abrogated erythropoietin (Epo)–independent erythroid colony formation evoked by Jak2V617F, a hallmark feature of PV. Re-expression of Stat5 in Stat5-deficient Jak2V617F knockin mice completely rescued the defects in transformation of hematopoietic progenitors and the PV phenotype. Together, these results indicate a critical function for Stat5 in the pathogenesis of PV. These findings also provide strong support for the development of Stat5 inhibitors as targeted therapies for the treatment of PV and other JAK2V617F-positive MPNs.

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Quantification and three-dimensional microanatomical organization of the bone marrow

Blood Advances ◽

10.1182/bloodadvances.2016003194 ◽

2017 ◽

Vol 1 (6) ◽

pp. 407-416 ◽

Cited By ~ 31

Author(s):

Cesar Nombela-Arrieta ◽

Markus G. Manz

Keyword(s):

Bone Marrow ◽

Blood Cells ◽

Structural Organization ◽

Imaging Techniques ◽

White Blood Cells ◽

Three Dimensional ◽

The Body ◽

Cellular Composition ◽

Spatial Logic ◽

Health And Disease

Abstract Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease.

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Megaloblastosis Produced by a Cytosine Antagonist

Blood ◽

10.1182/blood.v21.3.352.352 ◽

1963 ◽

Vol 21 (3) ◽

pp. 352-362 ◽

Cited By ~ 86

Author(s):

R. W. TALLEY ◽

V. K. VAITKEVICIUS

Keyword(s):

Bone Marrow ◽

Dna Synthesis ◽

Mechanism Of Action ◽

Cytosine Arabinoside ◽

Peripheral Blood ◽

Blood Cells ◽

White Blood Cells ◽

Structural Similarity ◽

Mitotic Abnormalities ◽

Temporary Decrease

Abstract 1. Cytosine arabinoside induced objective, but temporary, decrease of tumor masses in three patients with lymphosarcoma and slight decrease in some lesions in two out of ten treated patients with disseminated carcinomatosis. 2. In doses of 3 to 50 mg./Kg. given at varying intervals, cytosine arabinoside induced definite megaloblastic changes in the marrow of all patients studied. Mitotic abnormalities similar to those found in other megaloblastic anemias also occurred. 3. Associated with bone marrow changes, depressions of hemoglobin, white blood cells and platelets in the peripheral blood were observed. 4. The exact mechanism of action of cytosine arabinoside has not been elucidated. It is speculated that because of the close structural similarity between cytidylic acid, cytosine arabinoside could interfere with DNA synthesis.

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A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

Therapeutic Advances in Rare Disease ◽

10.1177/2633004020959349 ◽

2020 ◽

Vol 1 ◽

pp. 263300402095934

Author(s):

Morag Griffin ◽

Richard Kelly ◽

Alexandra Pike

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Life Expectancy ◽

Red Blood Cells ◽

Blood Cells ◽

Treatment Options ◽

White Blood Cells ◽

Paroxysmal Nocturnal Haemoglobinuria ◽

Complement Cascade ◽

Future Treatments

Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15 years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH. Lay summary Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are ‘stickier’ increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? • Eculizumab is an treatment given through a vein (intravenous) every week for 5 weeks then every 2 weeks after this, and has been available for 13 years, improving life expectancy to near normal. • Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8 weeks instead of every 2 weeks. In clinical studies it was comparable with eculizumab. • Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2 weeks to every 8 weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence. As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.

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