Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Trial of Thymoglobulin to Prevent Chronic Graft Versus Host Disease in Patients Undergoing Hematopoietic Progenitor Cell Transplantation (HPCT) From Unrelated Donors
Brief Summary: This is a randomized trial for patients undergoing hematopoietic progenitor cell transplantation (HPCT) from an unrelated donor. Approximately 50% of the patients enrolled will receive Thymoglobulin® as part of the preparative regimen prior to HPCT. The other 50% of the patients enrolled will receive a standard preparative regimen. Thymoglobulin is known to suppress the types of cells that can cause a transplant complication known as "chronic graft versus host disease (cGVHD)". The goal of this trial is to find out if adding Thymoglobulin to the preparative regimen will result in a decrease in cGVHD.


Options:
A: Inclusion Criteria:

* The recipient has a hematologic malignancy
* The recipient will receive one of the specified preparative regimens
* The recipient will receive either a bone marrow ("HPC, Marrow") or blood progenitor cell ("HPC, Apheresis") graft
* The recipient has an unrelated donor who with high resolution typing is either fully MHC matched at HLA-A, B, C and DRB1 with the recipient or is 1-antigen or 1-allele mismatched at A, B, C or DRB1 loci The recipient meets the transplant centre's criteria for unrelated donor allogeneic transplantation , either myeloablative or non-myeloablative (syn. RIC).
* The recipient has good performance status (Karnofsky ≥60%)
* Recipient has given signed informed consent For the questionnaire component only, be able to complete the questionnaires in English or with a validated translation (as posted on the project website)

Exclusion Criteria:

* The recipient is HIV antibody positive
* The recipient has a hypersensitivity to rabbit proteins or Thymoglobulin pharmaceutical excipients, glycine or mannitol
* The recipient has active or chronic infection (i.e. infection requiring oral or IV therapy)
* The recipient (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrollment
* The recipient (if female and of childbearing potential) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant
* The recipient (if male and fertile) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant
* For the questionnaire component only, the recipient is unable to participate due to cognitive, linguistic or emotional difficulties (i.e. the recipient can participate in the main study but will be excluded from the questionnaire component
B: Inclusion Criteria:

* Have undergone Allogeneic Stem Cell Transplanttaion (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
* Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
* Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day \[or equivalent prednisone dose 2.5 mg/kg/day\]), given alone or combined with calcineurin inhibitors (CNI) and either:

  * Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR
  * Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR
  * Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
* Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR
* Failure to taper the methylprednisolone dose to \<0.5 mg/kg/day (or equivalent prednisone dose \<0.6 mg/kg/day) for a minimum 7 days.

Exclusion Criteria:

* Has received more than one systemic treatment for steroid refractory aGvHD.
* Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
* Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus (HCV) based on assessment by the treating physician.
* Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
C: Inclusion Criteria:

PATIENT

1. Diseases

   Hematological malignancies confirmed histologically and not rapidly progressing:
   * AML in CR (defined as ≤ 5% marrow blasts and absence of blasts in the peripheral blood);
   * MDS with ≤ 5% marrow blasts and absence of blasts in the peripheral blood;
   * CML in CP;
   * MPS not in blast crisis and not with extensive marrow fibrosis,
   * ALL in CR;
   * Multiple myeloma not rapidly progressing;
   * CLL;
   * Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
   * Hodgkin's disease with chemosensitive disease.
2. Clinical situations

   * Theoretical indication for a standard allo-transplant, but not feasible because:

     * Age \> 50 yrs;
     * Unacceptable end organ performance;
     * Patient's refusal.
   * Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
3. Other inclusion criteria

   * Male or female; fertile patients must use a reliable contraception method;
   * Age \< 75 yrs;
   * Informed consent given by patient or his/her guardian if of minor age.

DONOR

* Related to the recipient (sibling, parent or child) or unrelated;
* Male or female;
* Any age;
* 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched;
* Weight \> 15 Kg (because of leukapheresis);
* Fulfills criteria for allogeneic PBSC donation according to standard procedures;
* Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

Exclusion Criteria:

PATIENT

* Any condition not fulfilling inclusion criteria;
* HIV positive;
* Non-hematological malignancy(ies) (except non-melanoma skin cancer) \< 3 years before nonmyeloablative HCT.
* Life expectancy severely limited by disease other than malignancy;
* Administration of cytotoxic agent(s) for "cytoreduction" within three weeks prior to initiating the nonmyeloablative transplant conditioning (Exceptions are hydroxyurea and imatinib mesylate);
* CNS involvement with disease refractory to intrathecal chemotherapy.
* Terminal organ failure, except for renal failure (dialysis acceptable)
* Uncontrolled infection;
* Karnofsky Performance Score \<70%;
* Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
* Patient is a female who is pregnant or breastfeeding;
* Previous radiation therapy precluding the use of 2 Gy TBI or 8 Gy TLI;

DONOR

* Any condition not fulfilling inclusion criteria;
* Unable to undergo leukapheresis because of poor vein access or other reasons.
D: Inclusion Criteria:

* Standard-risk of recipients with hematological malignancies (including AML-CR1, ALL-CR1, CML-CP, MDS-RA, RARS,RCMD,RAEB-1); age from 40 to 60; having HLA-matched sibling donor; Eastern Cooperative Oncology Group (ECOG)≤1, ejection fraction (EF)≥50%; bilirubin≤35µmol/L; AST, and ALT lower than or equall to two-fold baseline;creatinie≤130µmol/L.

Exclusion Criteria:

* Active, uncontrolled infection; severe allergy to ATG, including shock or laryngeal edema; secondary stem cell transplant recipient; haplidentical recipients; matched unrelated donor recipients; non-myeloablative condioning regimen recipients; EF\<50%; bilirubin\>35µmol/L; AST, and ALT higher than two-fold baseline; creatinie\>130µmol/L.

Answer: A