Please select the eligibility criteria that correspond to the clinical trial below.
Title: Allogeneic Hematopoietic Cell Transplantation With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings
Brief Summary: The present project aims at comparing two nonmyeloablative regimens currently used in 2 major HCT centers in the US for patients with HLA-matched related or unrelated donor: the one from the Seattle group consisting of 2 Gy TBI with fludarabine (90 mg/m²) versus the one from the Stanford group combining 8 Gy TLI with ATG.


Options:
A: 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.
B: 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
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:

Participation of patients in simultaneous diagnostic and comprehensive therapeutical trials for certain entities is allowed.

* Patients 18-60 years of age;
* Patients suffering from one of the following diseases:

  * AML: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
  * ALL: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
  * MDS, if transplantation is medically indicated: RA (with poor risk factors as classified by the International Prognostic Scoring System of MDS), RARS, RAEB, RAEB-t, CMML;
  * CML: beyond 1st chronic phase (CP1): accelerated phase, blast crisis, chronic phase (CP2, CP3);
  * OMF, if transplantation is medically indicated: Osteomyelofibrosis;
* Patients designated to undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation;
* Patients with a HLA-A, -B (DNA-based, 2 digits), HLA-DRB1, -DQB1 (DNA-based 4 digits) matched (8 out of 8 alleles) unrelated donor; serological typing is not required
* Patients with a Karnofsky Performance Score (KPS): \> 60%;
* Patients who underwent all obligatory screening examinations (special examinations within the last 4 weeks);
* Patients who have given their written informed consent to participate in the study.

Exclusion Criteria:

* Patients with significant cardiac (e.g. ejection fraction \<50%), pulmonary (e.g. FEV1 \<50%), renal (e.g. creatinine \> 1.5 mg/dl), metabolic (e.g. bilirubin \> 2.0 mg/dl) and/or CNS disease, currently uncontrolled by treatment, which may interfere with the completion of the study;
* Patients with any bacterial, viral, or fungal infections not under adequate antimicrobial control;
* Patients who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs-Ag), or Hepatitis C antibody, or who are known to have a positive result to the test of HIV antibodies;
* Patients with any additional concurrent or previous malignant disease;
* Patients with known hypersensitivity to rabbit immunoglobulin antibodies in past patient history or with known allergy to any substance chemically related to the study medication;
* Pregnant (β-HCG test) or lactating women;
* Patients who formerly underwent transplantation including previous autologous transplants;
* Patients who cannot communicate reliably with the investigator or who are not likely to cope with the requirements of the study.

Answer: C