GvHD prophylaxis in non-haploidentical allogeneic peripheral blood stem cell transplantation: beyond the standard to prevent relapse in patients with high-risk chronic lymphoproliferative diseases?

Abstract Abstract 2302 Although allogeneic peripheral blood stem cell transplantation from a matched related donor (RD-PBSCT) presents the best curable opportunity for many patients with hematologic malignancies, only about one third of individuals have HLA matched sibling donors. Fortunately, from unrelated donor peripheral blood stem cell transplantation has been acceptable and expanded recently. In order to evaluate the effect of allogeneic peripheral blood stem cell transplantation from unrelated donor (URD-PBSCT), we compare results of URD-PBSCT and RD-PBSCT that were done for 172 consecutive adult patients with hematologic maligancies from Jan 2002 to Dec 2008 at a single-center. Among these patients, 62 cases underwent URD-PBSCT and 110 cases underwent RD-PBSCT. Myeloablative conditioning was adopted for all patients. In graft versus host disease (GVHD) prophylaxis, 49 URD-PBSCT recipients received CSA, MTX, MMF and ATG (URD-ATG group), 13 recipients were given simulect more in base of URD-ATG group (URD-ATG+CD25 group) while RD-PBSCT recipients (RD group) received CSA, MTX and MMF. Engraftment was achieved in 98.4% of URD-PBSCT patients and 98.2% of RD-PBSCT patients (100% for patients surviving beyond 28 days after transplant). The cumulative incidence of acute GVHD (grade II-IV) was 15.4%, 36.7% and 29.1% respectively in the URD-ATG+CD25, URD-ATG and RD groups (P = 0.275). The cumulative incidence of chronic GVHD was 0%, 45.6%, 39.6% respectively and significant lower in URD-ATG+CD25 group than the other two groups (P = 0.0134). Relapse incidence was 53.8%, 12.2%, 14.5% respectively and significant higher in URD-ATG+CD25 group than the other s (P = 0.0059), while there was no different between the URD-ATG and RD groups (P = 0.610). Estimated overall survival (OS) at 5 years was 30.8%, 69.4% and 67.3% respectively and no significant difference between URD-ATG group and RD group (p=0.898). Adverse prognosis factors for relapse and OS included transplant not in remission and GVHD prophylaxis with simulect. Our results indicate PBSCT from unrelated donor may be considered comparable to those from related donor. Disclosures: No relevant conflicts of interest to declare.

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Low-Dose Azacitidine for Relapse of MDS/AML after Unrelated Donor Peripheral Blood Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.5034.5034 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5034-5034 ◽

Cited By ~ 1

Author(s):

James M. Rossetti ◽

Richard K. Shadduck ◽

Chandana Thatikonda ◽

Entezam Sahovic ◽

John Lister

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Peripheral Blood ◽

Low Dose ◽

Peripheral Blood Stem Cell ◽

Unrelated Donor ◽

Post Transplant ◽

Blood Stem Cell Transplantation

Abstract Background: Post-transplant relapse in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) is difficult to manage. Cytogenetic relapse and decreasing donor chimerism often precedes morphological relapse. Weaning of immunosuppressive agents and donor lymphocyte infusion (DLI) may induce graft versus tumor effect (GVT), but is of limited value for patients with existing GVHD. In addition, the degree of GVT in high-risk myeloid disease is suboptimal. We present our experience using low-dose azacitidine (AZA) for cytogenetic relapse post-transplantation. Methods: Six patients with high-risk myeloid malignancy with cytogenetic relapse after matched unrelated donor peripheral blood stem cell transplantation were treated with low-dose AZA at 25 mg/m2 SC or IV for 5 days. An average of 2 cycles of AZA were given (range = 1 to 3). There were 3 females and 3 males with a mean age of 48 years (range = 31 to 59 years). Four had high-grade MDS (including 2 with treatment related disease) and 2 had high-risk AML. Conditioning consisted of fludarabine and ablative doses of busulfan in all patients. Cytogenetic relapse was seen by FISH testing within 187 days post-transplant (range = 30 to 730 days). AZA was given after an initial attempt to wean immunosuppression, which was not possible in 3 patients due to existing GVHD. All patients tolerated AZA well, without major toxicity. DLI was possible in 3 patients following AZA. A reduction in cytogenetic abnormalities (by FISH) and increase in donor chimerism (by FISH or STR) was observed in 5 out of 6 patients (83%) within 21 days post-AZA (range = 7 to 71 days). Three of the 5 responders demonstrated improvement after 1 cycle. The other 2 responders improved after 2 cycles given 28 and 60 days apart, respectively. One of these patients responded to a second AZA cycle after failing DLI. AZA did not appear to induce or worsen GVHD in any patient. One patient remains in CR 4 months after 1 cycle of AZA. Another patient demonstrated ongoing improvement in chimerism until her death from previously existing GVHD 20 days after a third cycle of AZA. The remaining 3 responders relapsed within 30 days from time of first response (range = 17 to 43 days). Conclusions: Low-dose AZA appears to have activity in post-transplant relapse of MDS and AML. This low-dose regimen appears to be well tolerated, however, response to AZA is short-lived in the majority of patients. Further investigation is planned to improve the durability of response by giving AZA at regular intervals from the time of early relapse. The utility of AZA as a preparatory regimen pre-DLI should also be explored.

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