Treatment of relapsed acute myeloid leukemia with MLL/AF6 fusion after allogeneic hematopoietic stem cell transplantation with gemtuzumab ozogamicin with a long interval followed by donor lymphocyte infusion

Tamai, Hayato; Shioi, Yumiko; Yamaguchi, Hiroki; Okabe, Masahiro; Wakita, Satoshi; Mizuki, Taro; Nakayama, Kazutaka; Inokuchi, Koiti; Takagi, Kenji; Dan, Kazuo

doi:10.1038/sj.leu.2405029

Cited by 9 publications

(11 citation statements)

References 4 publications

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“…46,48,55 Incorporating novel drug combinations with allo-SCT or DLI Studies have shown that, gemtuzumab (GO) therapy is effective for patients with extramedullary relapse, which is considered a sanctuary site for the GVL effect. 56,57 The selectivity of GO for CD33 þ blast and progenitor hematopoietic cells makes it an attractive agent to use in post transplant relapse. GO is a recombinant humanized MoAb that targets the CD33 Ag that is expressed in more than 90% of myeloid malignancies.…”

Section: 55mentioning

confidence: 99%

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Management of relapse after allo-SCT for AML and the role of second transplantation

Savani

Mielke

Reddy

et al. 2009

Bone Marrow Transplant

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Relapse after allo-SCT for AML carries very poor prognosis. Second allo-SCT, although curative, is not an appropriate treatment option for a large number of relapsing patients (only 2-20% patients receive a second allo-SCT), and efforts to increase the number of patients who may benefit from a second allo-SCT are ongoing. In addition, understanding the varied biological processes that are operative in disease relapse has encouraged the development of novel therapies, and could be beneficial to patients who are currently managed conservatively with supportive care for relapsed disease. Incorporating novel combinations of drugs with immunomodulation, although theoretically attractive, should be tested in the setting of clinical trials. In this review, we discuss the currently available approaches for relapsed AML after allo-SCT.

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Section: 55mentioning

confidence: 99%

“…Recently, Tamai et al 57 used GO followed by DLI in a patient with post-allo-SCT relapse with prolonged remission, and the combination of GO and chemotherapy seems to be well tolerated. 58 Further studies are required to determine the effects of GO followed by DLI or GO with a second allo-SCT for advanced myeloid relapse after allo-SCT.…”

Section: 55mentioning

confidence: 99%

Management of relapse after allo-SCT for AML and the role of second transplantation

Savani

Mielke

Reddy

et al. 2009

Bone Marrow Transplant

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“…Studies in relapsed AML using different combinations of GO and chemotherapy, most commonly with ARA-C have resulted in variable results [4][5][6][7][8][9][10][11][12][13], while concerns of an increased hepatotoxicity risk in the pre-and postAllo-SCT setting have limited the use of GO in such cases. Nevertheless, case reports and small case series of GO monotherapy in AML patients relapsing after an Allo-SCT have reported on long-term remission in some patients and limited toxicity [14][15][16][17][18][19]. We therefore summarize our experience in testing the feasibility of administrating the combination of GO and intermediate dose cytarabine (ARA-C) as salvage therapy in a cohort of AML patients relapsing after Allo-SCT.…”

Section: Introductionmentioning

confidence: 99%

Salvage therapy with ARA-C and gemtuzumab ozogamicin in AML patients relapsing after stem cell transplantation

Koren‐Michowitz

Apel

et al. 2014

Ann Hematol

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Acute myeloid leukemia (AML) relapse is often associated with a poor outcome, especially after allogeneic stem cell transplantation (Allo-SCT). In patients relapsing early after SCT treatment, options are further limited by the fear for increased toxicity. We report our experience with ARA-C and gemtuzumab ozogamicin (GO) combination in relapsed post-SCT AML patients. Therapy consisted of ARA-C (1 gr/m(2)) for 4 days followed by one dose of GO 9 mg/m(2) on day 5 and was supported by donor stem cells when possible. Responding patients not developing graft versus host disease (GVHD) were eligible for immunotherapy with donor lymphocyte infusion (DLI) or a second Allo-SCT. Sixteen patients, median age 53 years (range 31-63), are included in this analysis. Patients underwent SCT for high-risk AML (n = 11) or AML relapse (n = 5), and 81 % had an early post-SCT relapse. Responses were achieved in 60 % of evaluable patients (CR-5 CRp-4). Median probabilities of survival (OS) and event-free survival (EFS) in the entire cohort, responding and non-responding patients were 103 and 76 days, 183 and 97 days, and 79 and 16 days, respectively. At 1-year follow-up, 25 % of patients were alive; however, all had relapse. Treatment resulted in grade 3-4 neutropenia and thrombocytopenia in all patients, and 27 % each had grade 3-4 hyperbilirubinemia or elevation of liver enzymes. One patient died during treatment due to intracranial hemorrhage. Of the six patients proceeding to second SCT or receiving DLI, three patients developed mild veno-occlusive disease (VOD). Combination therapy with ARA-C and GO after SCT results in short-term disease control and limited toxicity and could be considered for patients who are candidates for further immunotherapy.

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“…GO therapy has achieved a 30% response rate in patients with CD33-positive AML in their first relapse [3,4]. A few cases of acute leukemia successfully treated with GO in relapse after allo-SCT have previously been reported [5][6][7][8]. Of these, three cases maintained CR: two cases were treated with GO in combination with DLI [6,7], and one case showing extramedullary relapse was treated with GO alone, owing to the low tumor burden [8].…”

Section: Introductionmentioning

confidence: 99%

“…A few cases of acute leukemia successfully treated with GO in relapse after allo-SCT have previously been reported [5][6][7][8]. Of these, three cases maintained CR: two cases were treated with GO in combination with DLI [6,7], and one case showing extramedullary relapse was treated with GO alone, owing to the low tumor burden [8]. The remission duration of the former two cases was reported to be 240 days [6] and 18 months [7], respectively, and the latter to be 17 months [8].…”

Section: Introductionmentioning

confidence: 99%

Gemtuzumab ozogamicin-induced long-term remission in a woman with acute myelomonocytic leukemia and bone marrow relapse following allogeneic transplantation

et al. 2009

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A 56-year-old woman with acute myelomonocytic leukemia underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-SCT) from a matched unrelated donor in her first complete remission (CR). Veno-occlusive disease (VOD) prophylaxis consisted of low-dose heparin and ursodeoxycholic acid. Graft-versus-host disease (GVHD) prophylaxis comprised tacrolimus and short-term methotrexate. On day 14, VOD developed, but gradually resolved with supportive therapy. On day 58, she showed grade II acute GVHD, but this resolved spontaneously. On day 140, she developed hematological relapse with 40.2% marrow infiltration of CD33-positive blasts. Following the discontinuation of tacrolimus, gemtuzumab ozogamicin (GO) was administered. After GO administration, the patient exhibited mild VOD and severe pancytopenia with a sustained high fever for 6 weeks without evident infection. Bone marrow examination revealed severe hypoplastic marrow with 1.3% blasts 4 weeks after GO administration. Although transfusion-dependent pancytopenia persisted for 8 months after GO administration, bone marrow examination revealed the recovery of normal hematopoietic cells with 0.8% blasts. The patient has remained in CR with incomplete blood count recovery for 7 years following GO administration. Although the standard treatment for acute myeloid leukemia relapse after allo-SCT still remains to be established, GO may be a promising option.

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Treatment of relapsed acute myeloid leukemia with MLL/AF6 fusion after allogeneic hematopoietic stem cell transplantation with gemtuzumab ozogamicin with a long interval followed by donor lymphocyte infusion

Cited by 9 publications

References 4 publications

Management of relapse after allo-SCT for AML and the role of second transplantation

Management of relapse after allo-SCT for AML and the role of second transplantation

Salvage therapy with ARA-C and gemtuzumab ozogamicin in AML patients relapsing after stem cell transplantation

Gemtuzumab ozogamicin-induced long-term remission in a woman with acute myelomonocytic leukemia and bone marrow relapse following allogeneic transplantation

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