A Reduced Intensity Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.
Inclusion Criteria:
- At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy
or azacitidine or decitabine or tyrosine kinase inhibitor.
- Patients aged 18-70 years at initial referral with no available and suitably matched
related or unrelated donor.
- Acute myelogenous leukemia (AML):
- Complete first remission (CR1) at high risk for relapse as defined by:
- Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder;
- Therapy related AML;
- White cell count at presentation > 100,000;
- Presence of extramedullary leukemia at diagnosis;
- Any unfavorable sub type by FAB or WHO classification;
- High-risk cytogenetics (eg those associated with MDS, abnormalities of 5, 7, 8,
Philadelphia chromosome, complex karyotype)or high risk molecular abnormalities;
- Requirement for 2 or more inductions to achieve CR1.
- Any patient with newly diagnosed AML with intermediate risk cytogenetics.
- Any patient unable to tolerate consolidation chemotherapy as would have been deemed
appropriate by the treating physician.
- Complete second remission (CR2).
- Other acute leukemias that are ambiguous lineage or of other types eg blastic
plasmacytoid dendritic cell neoplasm in CR1 or CR2
- Acute lymphoblastic leukemia (ALL):
- lymphoblastic leukemia (ALL):
- Complete first remission (CR1) at high risk for relapse as defined by:
- White cell count at presentation > 30,000 for B-cell lineage and >100,000 for Tcell
lineage;
- Presence of a high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or
other MLL rearrangements (11q23)or other high-risk molecular abnormality;
- Failure to achieve complete remission after four weeks of induction therapy;
- Any patient with newly diagnosed ALL > or = to 50 years-old;
- Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would
have been deemed appropriate by the treating physician.
- Complete second remission (CR2).
- Myelodysplastic Syndrome (MDS):
- Intermediate-1 International Prognostic Scoring System (IPSS) score with poor risk
cytogenetics as defined by IPSS.
- Intermediate- 2 or High International Prognostic Scoring System (IPSS) score.
- MDS/ myeloproliferative disorder overlap syndromes.
- Any score with life threatening cytopenia(s), including red cell or platelet
transfusion dependence.
- Receipt of at least one cycle of cytotoxic chemotherapy, azacitidine or decitabine.
- MDS patients must have < or = to 5% bone marrow myeloblasts and ANC > or = to 0.5
(growth factor supported if necessary) at transplant work-up.
- Chronic myelogenous leukemia (CML) patients who have failed or are intolerant of
tyrosine kinase inhibitors.
- Any Non-Hodgkins lymphoma (including chronic lymphocytic leukemia) at high-risk of
relapse not suitable for either high dose myeloablative conditioning or
non-myeloablative conditioning
- Eligible patients with DLC NHL will:
have relapsed disease following initial therapy but failed to mobilize or had bone marrow
involvement and therefore are not suitable for an autologous transplant OR
- have failed an autologous transplant and be in CR after salvage chemotherapy.
- Eligible patients with transformed indolent NHL/CLL will:
have CR/PR of the large cell component of their disease after either salvage chemotherapy
or an autologous transplant.
- Eligible patients with mantle cell NHL will:
be high-risk as such as p53 positivity and be in 1st CR/PR after initial therapy OR have
relapsed disease following initial therapy and be in 2nd or 3rd CR/PR after salvage
chemotherapy.
- Eligible patients with indolent B cell NHL (such as, but not limited to, follicular,
small cell or marginal zone NHL) or CLL will have 2nd or subsequent progression
(pre-allograft cytoreduction necessary but CR/PR not required).
- Timing of UCBT:
- Admission for UCBT must be within an acceptable time period after the pre-allograft
chemotherapy. This will be defined as within 100 days of the start day of the last
cycle of chemotherapy (or decitabine or azacitidine) or other disease active agent).
- Organ Function and Performance Status Criteria:
- Karnofsky score > or = to 70 %.
- calculated creatinine clearance > or = to 60 ml/min
- bilirubin < than or = to 1.5 mg/dL, ALT < than or = to 3 x upper limit of normal
unless benign congenital hyperbilirubinemia,
- pulmonary function (spirometry and corrected DLCO) > or = to 50% normal.
- left ventricular ejection fraction > or = to 50%.
- albumin > or = to 3.0.
- Graft Criteria:
- 2 UCB units selected according to current MSKCC unit selection algorithm. HLA testing
to be done using molecular techniques: A and B antigen to at least intermediate
resolution and DRB1 allele at high-level resolution.
- Each unit will be at least 4/6 HLA-A, B antigen and DRB1 allele matched with the
recipient.
- In addition, each unit will have a cryopreserved dose of at least 2.0 x 10^7 total
nucleated cells/recipient body weight (TNC/kg).
- Units with attached segments for confirmatory typing will be given preference.
Exclusion Criteria:
- Diagnosis: acute leukemia in morphologic relapse or with morphologic persistent
disease (cytogenetic or molecular persistence/relapse in morphologic CR are
eligible); MDS or CML or other myeloproliferative disorder with > 5% blasts.
- Prior allogeneic transplant.
- Active and uncontrolled infection at time of transplantation.
- HIV infection.
- Inadequate performance status/ organ function.
- Pregnancy or breast feeding.
- Patient or guardian unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, follow-up and research
tests.