To test a new agent, LBH589, in combination with glucocorticoids as initial therapy of acute graft versus host disease (GVHD).

Dose escalation study to test the safety (Phase I), pharmacology and preliminary clinical activity (Phase II) of a Novel histone deacetylase (HDAC) inhibitor, LBH589, in the treatment of the following GVHD presentations: Classic, Late-onset acute GVHD, Recurrent acute GVHD, Overlap syndrome.

Inclusion Criteria:

1. Patients receiving allogeneic hematopoietic cell transplantation (HCT) with peripheral blood, bone marrow or cord blood stem cells regardless of initial diagnosis who develop a clinical diagnosis of acute GVHD as defined in Section 2 diagnosed and treated with systemic glucocorticoids within 72 hours prior to enrollment. Biopsy of involved skin and gastrointestinal tract is strongly encouraged, but not required for study entry. For patients with aspartic transaminase (AST) or alanine transaminase (ALT) or Alkaline phosphatase with gamma-glutamyltransferase (GGT) elevations without bilirubin elevation must have a liver biopsy to document GVHD diagnosis. Patients should meet one of the following criteria:

   If GVHD is present in an isolated organ:

   1. Skin rash involvement of a minimum of 50% of body surface area in absence of documented drug allergy or infectious etiology.
   2. Diarrhea with a minimum stool volume of 500 mL/day and/or a minimum of 2 stools above baseline/day in absence of enterocolitis from C. difficile or other documented pathogens.
   3. Increase in bilirubin above upper limit of normal (ULN) in absence of clinically defined veno-occlusive disease.
   4. Isolated increased AST and/or ALT and/or increased alkaline phosphatase above ULN with GGT elevation above ULN with documented liver GVHD biopsy.

   If GVHD presentation involves >/= 2 organs: GVHD Grade >/= II as defined in Table D of protocol.

2. Male or female patients aged 18 or older at time of enrollment

3. Signed informed consent

4. Absolute neutrophil count (ANC) greater than 500/μL, platelets >/= 20 x 10^9/L supported by platelet transfusion and hemoglobin >/= 8 g/dl supported by red cell transfusion.

5. Calculated creatinine clearance (CrCl) >/= 30 mL/min (MDRD Formula)

6. Serum potassium >/= lower limit of normal (LLN), Total serum calcium [corrected for serum albumin] or ionized calcium >/= LLN, Serum magnesium >/= LLN and Serum phosphorus >/= LLN on the day of LBH589 administration

7. Thyroid-stimulating hormone (TSH) </= ULN and free T4 within normal limits at the time of patient enrollment within baseline laboratories. Patients are permitted to receive thyroid hormone replacement to treat underlying hypothyroidism

8. Baseline multiple gated acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) >/= the lower limit of the institutional normal before transplantation.

Exclusion Criteria:

1. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24 hrs of receiving the first dose of study medication if a pregnancy test was not done pre-transplant. Male patients whose sexual partners are WOCBP not using effective birth control

2. Patients requiring mechanical ventilation support.

3. Active, uncontrolled life threatening viral or fungal disease, such as cytomegalovirus (CMV) pneumonia or gastroenteritis, Aspergillus pneumonia or brain abscess. For bacterial or viral infections, patients must be receiving therapy and have no signs of progression for 48 hours prior to enrollment. For fungal infection patients must be receiving systemic anti-fungal therapy and have no signs of progression for 1 week prior to enrollment. Progressing infection is defined as hemo-dynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infections. Persisting fever without other signs of symptoms will not be interpreted as progressing infections.

4. Receipt of other investigational new drugs for GVHD including agents used for GVHD prophylaxis within 30 days. The following agents are not considered experimental and therefore are not excluded: cyclosporine, tacrolimus, sirolimus, glucocorticoids, antithymocyte globulin, replacement corticosteroid therapy for hypoadrenalism and methotrexate.

5. HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days.

6. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment.

7. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:

   1. Patients with congenital long QT syndrome.
   2. History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of a controlled atrial arrhythmia are eligible).
   3. Any history of ventricular fibrillation or torsade de pointes.
   4. Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm.
   5. Patients are excluded if the average of the QT Corrected by the Fridericia Formula (QTcF) is > 470 msec on the screening EKGs.
   6. Right bundle branch block + left anterior hemiblock (bifascicular block).
   7. Patients with myocardial infarction or unstable angina \