• overall response(ORR) [ Time Frame: 1 Year post-autograft ]
  ORR is defined as the proportion of subjects who achieve PR to better rate, according to the IMWG criteria
• overall survival(OS) [ Time Frame: 1 Year post-autograft ]
  OS is defined as the duration from the data of registration to death.If the subject is alive, the data will be censored as being alive; the vital status is unknown as last known.
• Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease [ Time Frame: 1 year post-allograft ]
  aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999). GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death cGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
• Non-relapse Mortality (NRM) [ Time Frame: 1 year post-allograft ]
  Number of patients with non-relapse mortalities
• Number of Patients Who Had Infections [ Time Frame: 1 Year post-autograft ]
  Number of patients who had infections

• Multiple Myeloma
• Plasma Cell Leukemia
• Extramedullary Plasmacytoma
• Loss of Chromosome 17p
• t(14;16)
• t(4;14)
• T(14;20)
• 1Q21 Amplification
• Complex Karyotype

• Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  Allogeneic Stem Cell Transplant: Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients.
  Other Names:

  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HCT
  • SCT
• Procedure: Autologous Hematopoietic Stem Cell Transplantation x 1 or x 2
  Autologous hematopoietic stem cell transplantation :Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day followed collecting CD34+ peripheral blood stem cells . Day 0 Infusion of autologous stem cells. Patients during 3-6 months after the 1st SCT will undergo a 2nd SCT. Patients who had not enough PBSC will undergo a 1st SCT.
  Other Name: autologous stem cell transplantation
• Drug: Melphalan Given IV
  conditioning regimen: autologous ARM: Day -2 Melphalan 200 mg/m^2/day IV over 30 minutes. allogeneic ARM: Day -4, Day -3 Melphalan 70 mg/m^2/day IV over 30 minutes
  Other Name: Alkeran
• Drug: Fludarabine Injection
  conditioning regimen:Days -6,-5,-4,-3 Fludarabine 30 mg/m^2/day IV
  Other Name: Fludara
• Drug: PI and dexamethasone as maintenance therapy
  Bortezomib and dexamethasone(VD),Ixazomib and dexamethasone(ID)
  Other Names:

  • VD
  • ID
• Drug: PI+IMids+Dexamethasone as Consolidated Chemotherapy
  Oral lenalidomide at the starting dose of 25mg on days 1-21 every 28 days or days 1-14 every 21 days. Dexamethasone at 20mg twice weekly on days 1,2,4,5,8,9,11&12 of each 21-day.
  Other Names:

  • VRD
  • IRD
  • VDPACE
  • VDECP

• Experimental: A:Allogeneic Stem Cell Transplant Group
  Fludarabine+Melphalan followed by Allogeneic SCT.
  Interventions:

  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Drug: Melphalan Given IV
  • Drug: Fludarabine Injection
  • Drug: PI and dexamethasone as maintenance therapy
• Experimental: B:Autologous Stem Cell Transplant
  Melphalan followed by Autologous SCT.
  Interventions:

  • Procedure: Autologous Hematopoietic Stem Cell Transplantation x 1 or x 2
  • Drug: Melphalan Given IV
  • Drug: PI and dexamethasone as maintenance therapy
• Experimental: C:Non-Transplant
  Consolidated Chemotherapy for Patients Unable to Receive Transplantation
  Interventions:

  • Drug: PI and dexamethasone as maintenance therapy
  • Drug: PI+IMids+Dexamethasone as Consolidated Chemotherapy

Inclusion Criteria:

1. Clinical diagnosis of high-risk multiple myeloma

   In addition, patients must meet at least one of the following criteria I-IX (I-VIII at time of diagnosis or pre-autograft):

   I.Complex karyotype

   II.Fluorescent in situ hybridization (FISH) translocation 4:14 or 14:16,

   III.FISH translocation 1q21,

   IV.FISH deletion 17p,

   V.R-ISS III stage,

   VI.Two or more high-risk cytogenetic abnormalities exist

   VII.Plasma cell leukemia

   VIII.Extramedullary plasmacytoma

   IX.Recurrent or non-responsive (less than partial remission [PR]) MM after at least 4 cycles of PI/IMids-based chemotherapy

2. candidate for high-dose chemotherapy with stem cell transplantation
3. ECOG performance status score of 0,1,or2 -

Exclusion Criteria:

1. The current diagnosis of smoldering multiple myeloma, monoclonal gammopathy of undetermined significance of disease, Waldenstr o m macroglobulinemia.
2. during the first 5 years of the study, there were no other malignancies, including basal cell carcinoma or in situ cervical cancer.
3. according to the National Cancer Institute general toxicity criteria (NCI CTC), subjects had peripheral neuropathy of grade 2 or above:
4. were enrolled within 6 months before had a myocardial infarction, or New York Heart Association (NYHA) III or IV heart failure ,uncontrolled angina, uncontrolled severe ventricular arrhythmias or ECG evidence of acute ischemia or conduction system abnormalities and activity the clinical significance of pericardial disease, or cardiac amyloidosis -