• Incidence of regimen-related toxicity [ Designated as safety issue: Yes ]
• Incidence of acute and chronic graft-versus-host-disease [ Designated as safety issue: No ]
• Incidence of relapse [ Designated as safety issue: No ]

• Incidence of regimen-related toxicity [ Designated as safety issue: Yes ]
• Incidence of acute and chronic graft-versus-host-disease [ Designated as safety issue: Yes ]
• Incidence of relapse [ Designated as safety issue: No ]

RATIONALE: Giving chemotherapy drugs, such as cytarabine and mitoxantrone, before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, and methylprednisolone before or after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best way to give high-dose cytarabine together with mitoxantrone in treating patients with juvenile myelomonocytic leukemia undergoing a second donor stem cell transplant.

OBJECTIVES:

Primary

• To determine the incidence of 1-year disease-free survival in patients with juvenile myelomonocytic leukemia and who is undergoing a repeat stem cell transplantation.

Secondary

• To evaluate the incidence of regimen-related toxicity.
• To evaluate the incidence of acute and chronic graft-versus-host-disease.
• To evaluate the incidence of relapse.

OUTLINE:

• Preparative cytoreductive therapy: Patients receive high-dose cytarabine IV over 2 hours on days -9 to -4 and mitoxantrone hydrochloride IV over 30 minutes on days -9 to -7.
• Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients undergoing umbilical cord blood transplantation receive methylprednisolone (as graft failure prophylaxis) IV twice daily on days 5 to 19 followed by a taper every other day thereafter until day 25.
• Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours every 8-12 hours or orally twice daily beginning on day -3 and continuing until day 50, followed by a taper to day 90, in the absence of GVHD. Patients undergoing nongenotypically identical bone marrow transplantation also receive methotrexate IV on day 1 beginning 24 hours after completion of stem cell infusion and on days 3, 6, and 11.
• Post-transplantation isotretinoin therapy: Patients receive oral isotretinoin once daily beginning on day 60 and continuing until 1 year after HSCT.

Patients undergo bone marrow sample collection on day 21, day 60, day 100, at 6 months, and at 1 year for chimerism studies. Patients also undergo blood sample collection periodically to monitor peripheral blood counts for immune reconstitution.

After completion of study treatment, patients are followed on day 21, day 100, at 6 months, and at 1 year.

• Drug: cyclosporine
• Drug: cytarabine
• Drug: isotretinoin
• Drug: methotrexate
• Drug: methylprednisolone
• Drug: mitoxantrone hydrochloride
• Procedure: allogeneic bone marrow transplantation
• Procedure: allogeneic hematopoietic stem cell transplantation
• Procedure: umbilical cord blood transplantation

DISEASE CHARACTERISTICS:

• Diagnosis of juvenile myelomonocytic leukemia (JMML)

• Relapsed or residual disease after initial allogeneic hematopoietic stem cell transplantation (HSCT)

  • Relapsed* disease as evidence by the reappearance of all of the following:

    • Leukocytosis with absolute monocytosis > 1 x 10^8/L
    • Presence of immature myeloid cells in the peripheral circulation in two consecutive bone marrow specimens taken ≥ 1 month apart
    • Presence of clonal cytogenetic abnormalities NOTE: *Diagnosis of relapse will be supported by the return of an abnormal cytogenetic marker (if present at diagnosis) or the presence of host cells by restriction fragment length polymorphism or other method.
  • Residual disease is defined as failure to eradicate original disease without prior documentation of remission

• Patients should be ≥ 6 months from first HSCT, if clinically stable

  • In patients with rapidly progressive JMML, second HSCT may be performed earlier
• Available donor should be the same type as used in the initial HSCT or a greater HLA-disparate donor to enhance possibility of graft-versus-leukemia

• Stem cell source may be allogeneic bone marrow or umbilical cord blood

  • Cord blood units selected for transplantation must contain ≥ 1 x 10^7 nucleated cells/kg patient body weight

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 70-100% or Lansky PS 50-100%
• Ejection fraction ≥ 45%
• FEV_1 > 50%
• DLCO > 50%
• Creatinine clearance ≥ 40 mL/min
• No clinical evidence of hepatic failure (e.g., coagulopathy or ascites)
• No active uncontrolled infection within 1 week of HSCT

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics