Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prophylaxis of Chronic Graft-versus-host Disease (cGvHD) With or Without Anti-T-lymphocyte-globulin (ATG Fresenius) Prior Allogeneic Peripheral Stem Cell Transplantation From HLA-identical Siblings After Myeloablative Conditioning in Patients With Acute Leukemia: A Randomized Phase III-study
Brief Summary: This multicenter, prospective phase III-study is to compare the administration of ATG FRESENIUS to the NON-administration of ATG FRESENIUS in a myeloablative conditioning regimen followed by allogeneic hematopoeitic stem cell transplantation from an HLA-identical sibling in patients with acute Leukemia. This clinical trial is to show that the administration of ATG FRESENIUS reduces the risk of chronic Graft-versus-Host disease after allogeneic stem cell transplantation from HLA-identical siblings.


Options:
A: Inclusion Criteria:

* Have undergone allogeneic stem cell transplantation (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
* Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) \> 1000/mm\^3 and platelet count \> 25,000/ mm\^3
* Participants with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria prior to randomization:

  * Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1
  * Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3
* Participants currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of \< 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as follows:

  * A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR
  * Disease persistence without improvement despite continued treatment with prednisone at \> 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR
  * Increase to prednisolone dose to \> 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
* Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib

Exclusion Criteria:

* Participants who have received 2 or more systemic treatment for cGvHD in addition to corticosteroids ± CNI for cGvHD
* Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment

  \* Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
* Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
* Failed prior alloSCT within the past 6 months from Cycle 1 Day 1
* Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
* Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible
* Any corticosteroid therapy for indications other than cGvHD at doses \> 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
B: 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.
C: 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
D: Inclusion Criteria:

* Acute myeloid leukemia in first or subsequent complete remission (de-novo or secondary AML)
* Acute lymphoblastic leukemia in first or subsequent complete remission
* Patient's age: 18 - 65 years
* Myeloablative standard conditioning
* HLA-identical sibling (HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1)
* No major organ dysfunctions
* Patient's written consent

Exclusion Criteria:

* No complete remission at time of randomization
* Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as

  * Total bilirubin, SGPT or SGOT 5 times upper the normal level
  * left ventricular ejection fraction \<30%
  * Creatinine clearance \<30 ml/min
  * DLCO \<35% and/or receiving supplementary continuous oxygen
* Positive serology for HIV
* Pregnant or lactating women
* Serious psychiatric or psychological disorders
* Progressive invasive fungal infection at time of registration

Answer: D