• Protocol 260 - Response by Day 28, also called Overall Response. Overall response. includes complete response (CR) and partial response (PR) [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
• Protocol 261- Patients were followed for 2 years for safety. The incidence rate of different adverse events among subjects treated with either dose of Prochymal® in the preceding study (Protocol No. 260). [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

• Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1, [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
• Protocol 260 - Time to best response of GVHD [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
• Protocol 260 - Time to improvement of GVHD in one or more organs [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
• Protocol 261 - Survival through study day 90 [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

To establish the safety and efficacy of two dose levels of Ex-vivo Cultured Adult HumanMesenchymal Stem Cells (Prochymal) in subjects experiencing acute GVHD, Grades II-IV,post HSC transplant.

Protocol 260 - Subjects will be randomized with equal probability to the treatment arms (2 million cells/kg of Prochymal or 8 million cells/kg of Prochymal) using a stratified block design. The stratification factor is acute GVHD grade. For the purpose of stratification, the GVHD grades are II and III-IV. Treatment with investigational agent was administered on study Days 1 and 4. Patients were followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurred first.

Protocol 261 - Subjects were evaluated for safety until 2 years from Day 1 of the preceding Prochymal® Protocol No. 260 until withdrawal or death.

• Drug: Prochymal - 2 million cells
  2 million cells/kg actual body weight, intravenously on study Days 1 and 4
  Other Names:

  • Ex-vivo Cultured Adult Human Mesenchymal Stem Cells
  • hMSCs
• Drug: Prochymal - 8 million cells
  8 million cells/kg actual body weight intravenously on study Days 1 and 4
  Other Names:

  • Ex-vivo Cultured Adult Human Mesenchymal Stem Cells
  • hMSCs

• Prochymal - 2 million cells: Active Comparator
  Prochymal - 2 million cells/kg actual body weight, intravenously on study Days 1 and 4 plus daily methylprednisolone 2 mg/kg intravenously or prednisone 2.5 mg/kg orally. Subjects will also continue cyclosporine, tacrolimus, and/or MMF at full therapeutic doses
  Intervention: Drug: Prochymal - 2 million cells
• Prochymal - 8 million cells: Active Comparator
  Prochymal - 8 million cells/kg actual body weight intravenously on study Days 1 and 4 plus daily methylprednisolone 2 mg/kg intravenously or prednisone 2.5 mg/kg orally. Subjects will also continue cyclosporine, tacrolimus, and/or MMF at full therapeutic doses
  Intervention: Drug: Prochymal - 8 million cells

• Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002 Jan;30(1):42-8.
• Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. Review.
• Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005 May;11(5):389-98.
• Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41.
• Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45.

Protocol 260 Inclusion Criteria:

• Subjects must be 18 to 70 years of age inclusive
• If female and of child-bearing age, subjects must be non-pregnant, not breast feeding, and use adequate contraception. Males must use adequate contraception.
• Subject must have newly diagnosed, Grade II-IV acute GVHD requiring therapy. Biopsy for confirmation of GVHD is not mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting biopsy results.
• Subject must have received either full or reduced intensity myeloablative regimens followed by an allogeneic hematopoietic stem cell transplant using bone marrow, peripheral blood stem cell, or cord blood, including DLI

• Subjects must have minimal renal and hepatic function as defined by:

  * Calculated creatinine clearance (CLcr) of > 30 mL/min using the Cockroft-Gault equation

• Subject must be available for all specified assessments at the study site through study Day 28.
• Subjects must provide written informed consent and authorization for use and disclosure of protected health information (PHI).

Protocol 260 Exclusion Criteria:

• Subject has received previous treatment for Grade II-IV acute GVHD (except as noted in criterion 2).
• Subject has been treated for GVHD with methylprednisolone, > 2mg/kg/day, for more than 72 hours prior to receiving Prochymal™
• Subject has uncontrolled alcohol or substance abuse within 6 months of randomization.
• Subject has received an investigational agent (not approved by FDA for marketed use in any indication) within 30 days of randomization. Subjects may not receive an investigational agent during the 28-day study period
• Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject (e.g., uncontrolled infection, right heart failure, pulmonary hypertension, etc.)
• Subject has unstable arrhythmia
• Subject is unwilling to sign consent form for the long-term follow-up study, protocol No. 261
• Subject has a known allergy to bovine or porcine products.
• Subject had received transplant for a solid tumor disease.

Protocol 261 Inclusion Criteria:

• Subject must have received any treatment with the Investigational Agent in the preceding Prochymal® study.
• Subject must have completed their participation in a preceding Prochymal® study.
• If female and of child-bearing age, subjects must be non-pregnant, not breast-feeding, and use adequate contraception. Male subjects must use adequate contraception.
• Subject must provide written informed consent and written authorization for disclosure and use of PHI.