Conditioning regimen, GVHD prophylaxis and treatment
The majority (n=188; 82%) of the patients underwent myeloablative allogeneic HCT,
and the rest 42 patients received non myeloablative-reduced intensity conditioning
regimen. The most common conditioning regimens used for myeloablation were
either BUCY or TBICY. The myeloablative chemotherapy (MAC) regimen BUCY
consisted of busulphan (po BU; 4 mg/kg /day for 4 days; or iv BU formulation 3.2
mg/kg/day for 4 days and cyclophosphamide CY; 60 mg/kg/day for 2 days. The
radiation containing regimen comprised of fractionated TBI (FTBI) to a total dose of
1440 cGy followed by cyclophosphamide (total dose 120 mg/kg). All patients had
protective lung shielding. Customized lung blocks were used to reduce the lung dose
to 12 Gy. Antithymocyte globulin (ATG) usually rabbit (2.5 mg/kg) on day -3 and -2
or in few cases MabCampath was given before HCT to patients with unrelated donors.
Patients with severe aplastic anemia were prepared with CY at 50 mg/kg/day for 4
days (total dose 200 mg/kg) and ATG at 2.5 kg/day for 4 days (total dose 10 mg/kg).
In patients not in remission at the time of transplantation Thiotepa (250 mg/m 2 for 3
days, total dose 750 mg/ m2) or Etoposide (60mg/kg) was added to modified BUCY.
Patients with mantle cell lymphoma or those with other malignancy, ineligible for
conventional allogeneic HCT received a reduced intensity conditioning (RIC)
regimen consisting of fludarabine (FLU; 30 mg/kg/day for 5 days, total dose
150mg/kg) plus either CY (60 mg/kg/day for 2 days) or BU (4 mg/kg/day for 2 days,
total dose 8 mg/kg) associated with ATG (2.5 mg/kg/day for 2-3days).
Acute GVHD was assessed and graded according to the criteria of Glucksberg et al3.
Chronic GVHD was diagnosed and graded according to the criteria of Sullivan et al4.
The most widely used prophylactic regimen for GVHD was the combination of a
calcineurin inhibitor (cyclosporine or tacrolimus) with short-term methotrexate post
MAC regimen, whereas cyclosporine plus mycophenolate mofetil post RIC regimen.
Tacrolimus, possibly more effective than CSP, was administered in unrelated HCTs.
Cyclosporine, tacrolimus, and creatinine levels were monitored after HCT and dose
adjustments were made in case of excessive increase in creatinine levels, or toxic
levels of the calcineurin inhibitor. If no active GVHD was present, cyclosporine was
discontinued within 3-6 months after HCT. Treatment for cGVHD consisted of
methylprednisolone and re-administration of CSP, if already withdrawn. In corticoresistant GVHD, several combinations of immunosuppressive drugs and ECP
(extracorporeal photopheresis) were used.
Supportive treatment
Infection prophylaxis consisted of acyclovir and trimethoprim-sulphamethoxazole for
Pneumocystis jiroveci infection. Low-dose liposomal amphotericin B or voriconazole
or caspofungin was given for prophylaxis or in case of history of aspergillosis. Preemptive treatment with ganciclovir, foscarnet or valganciclovir was given for patients
with cytomegalovirus (CMV) reactivation detected by molecular methods.