Nonmyeloablative Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies With Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression With Cyclophosphamide Administered Before and After Transplantation.
Inclusion Criteria:
- Patients ≤70 years old
- Eligible diagnoses:
- CML in AP
- AML with high-risk cytogenetics [del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q,
21q, 17p, t(6:9), t(9;22), complex karyotypes (≥3 abnormalities)] in CR1
- AML ≥ CR2; patients should have <5% marrow blasts at the time of transplant
- High-risk ALL defined as:
CR1 with high-risk cytogenetics t(9;22), t(8;14), t(4;11), t(1;19) for adult patients >4
wk to achieve CR1
≥ CR2 Patients should have <5% marrow blasts at the time of transplant
- MDS (>int-1 per IPSS) after ≥ 1 prior cycle of induction chemotherapy; should have<5%
marrow blasts at the time of transplant
- MM Stage II or III patients who have progressed after an initial response to
chemotherapy or autologous HSCT or MM patients with refractory disease who may
benefit from tandem autologous-nonmyeloablative allogeneic transplant
- CLL, NHL or HD who are ineligible for autologous HSCT or who have
resistant/refractory disease and who may benefit from tandem autologous
nonmyeloablative allogeneic transplant.
- Patients who have received a prior allogeneic HSCT and who have either rejected their
grafts or who have become tolerant of their grafts with no active GvHD requiring
immunosuppressive therapy could be enrolled
Exclusion Criteria:
- Patients with suitably matched related or unrelated donors
- Patients with conventional transplant options (a conventional transplant should be
the priority for eligible patients ≤ 50 yr of age who have a related donor mismatched
for a single HLA-A, -B or DRB1 antigen)
- CNS involvement with disease refractory to intrathecal chemotherapy
- Presence of active, serious infection (e.g., mucormycosis, uncontrolled
aspergillosis, tuberculosis)
- Karnofsky Performance Status < 60% for adult patients (Appendix A)
- Patients with the following organ dysfunction:
- Left ventricular ejection fraction <35%
- DLCO <35% and/or receiving supplemental continuous oxygen
- Liver abnormalities: fulminant liver failure, cirrhosis of the liver with
evidence of portal hypertension, alcoholic hepatitis, esophageal varices,
hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced
by prolongation of the prothrombin time, ascites related to portal hypertension,
bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis
with total serum bilirubin >3 mg/dL or symptomatic biliary disease.
- HIV-positive patients
- Women of childbearing potential who are pregnant (β-HCG+) or breast feeding
- Fertile men and women unwilling to use contraceptives during and for 12 months post
transplant
- Life expectancy severely limited by diseases other than malignancy
- Patients on any other investigational drug at time of enrolment