Please select the eligibility criteria that correspond to the clinical trial below.
Title: The CAD5 Study::Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicenter Trial on the Safety and Efficacy of Bendamustine and Rituximab Combination Therapy
Brief Summary: Prospective, non-randomized multicenter study on the safety and efficacy of combination therapy with bendamustine and rituximab for chronic cold agglutinin disease.


Options:
A: Inclusion Criteria:

* Individuals at least 18 years of age
* Diagnosis of CAD defined by the combination of chronic hemolysis, cold agglutinin titer (IgM or IgA) \>64 at 4°C, positive direct antiglobulin test (DAT) when performed with polyspecific antiserum, negative (or only weakly positive) anti-IgG, and strongly positive with anti-C3d
* LDH level \> 2 x upper limit of normal (ULN)
* Clinical symptoms requiring treatment, such as anemia, anemia-related symptoms or hemolysis-related symptoms
* Sufficient supplementation of iron, folic acid and vitamin B12 prior to treatment phase
* Patient must be willing and able to give written informed consent;
* Patients must be vaccinated against N. meningitidis at least 14 days prior treatment
* Patient must avoid conception during the trial using a method that is most appropriate for their physical state and culture

Exclusion Criteria:

* Active aggressive lymphoma requiring therapy or an active non-lymphatic malignant disease other than basal cell carcinoma or CIS of the cervix
* Liver disease with elevated LDH
* Absolute neutrophil count \< 500/µL
* Presence or suspicion of active bacterial or viral infection, in the opinion of the Investigator, at treatment start or severe recurrent bacterial infections
* Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
* Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-treatment Phase
* History of bone marrow/stem cell transplantation
* Inability to cooperate or any condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study
* Hypersensitivity to eculizumab, to murine proteins or to one of the excipients
B: Inclusion Criteria:

1. CAD diagnosis defined by the combination of -

   1. Chronic hemolysis
   2. Cold agglutinin titer 64 or higher
   3. Positive direct antiglobulin test when performed with polyspecific antiserum, negative (or only weakly positive) with anti-IgG, and strongly positive with anti-C3d
2. The presence of a clonal B-cell lymphoproliferative disorder defined by -

   1. Monoclonal band by serum electrophoresis with immunofixation, and/or
   2. CD20 positive lymphocyte population with cellular kappa/lamda-ratio higher than 3.5 or less than 0.9, using flowcytometric immunophenotyping of bone marrow aspirates
3. Indication for therapy, i.e. significant anemia and/or considerable cold-induced circulatory symptoms
4. Written informed consent

Exclusion Criteria:

1. An aggressive lymphoma
2. Non-lymphatic malignant disease other than basal cell carcinoma of the skin. A history of probably cured cancer is not an exclusion criterion.
3. Known HIV infection
4. Acute or chronic hepatitis B or C
5. Liver failure or active parenchymal liver disease. Bilirubin levels higher than 51 mol/L (3.0 mg/dL) when due to hepatic impairment. Elevated serum bilirubin level due to hemolysis is not an exclusion criterion.
6. Pregnancy or breast-feeding
7. Patients of childbearing age who are not willing to use safe contraception during the entire study period and 6 months following its cessation
8. All contraindications to the study drugs will be regarded as exclusion criteria.
9. Age below 18 years
10. Inability to cooperate
C: Inclusion criteria:

* Participants greater than or equal to (\>=)18 years of age
* Have been diagnosed with warm autoimmune hemolytic anemia (wAIHA) for at least 3 months, and are currently receiving treatment for wAIHA or have previously received treatment for wAIHA (treatment-naive participants are not eligible)
* Participants must be able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures

Exclusion criteria:

* Participants must not be pregnant or breastfeeding
* Participants must not have other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate
* Have been diagnosed with cold antibody autoimmune hemolytic anemia (AIHA), cold agglutinin syndrome, mixed type (that is, warm and cold) AIHA, or paroxysmal cold hemoglobinuria
D: Inclusion Criteria:

* Newly diagnosed "warm" or "cold" AIHA, defined by symptomatic anemia and positive DAT, in the absence of underlying lymphoproliferative, infectious or neoplastic disease (according to the single Center diagnostic criteria).
* Idiopathic "warm" or "cold" AIHA relapsed after first line treatment with oral prednisone.
* Aged \>18 years
* ECOG performance status grade 0, 1 or 2
* No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
* Patients who have provided written informed consent prior to study participation, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.

Exclusion Criteria:

* Cell or humoral immunologic deficit (congenital or acquired)
* Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
* Active bacterial, viral, or fungal infection requiring systemic therapy HIV or HbsAg positive (with HBV-DNA+) or HCV-Ab positive (with HCV-RNA+) patients
* History of malignancies within 3 years prior to study entry
* Concomitant immunosuppressive or cytotoxic treatment
* Positive pregnancy test. Lactation.
* The presence of associated organ-specific autoimmune diseases do not constitute exclusion criteria. Previous splenectomy does not constitute exclusion criteria

Answer: B