Leukemia & Lymphoma

ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20

Use of High-Dose Cytarabine in Autologous Bone Marrow Transplantation in Acute Myeloid Leukemia Ruggero Mozzana, Aldo Della Volpe, Chiara Butti, Vittorio Fossatif, Silvana Selva & Giorgio Lambertenghi Deliliers To cite this article: Ruggero Mozzana, Aldo Della Volpe, Chiara Butti, Vittorio Fossatif, Silvana Selva & Giorgio Lambertenghi Deliliers (1992) Use of High-Dose Cytarabine in Autologous Bone Marrow Transplantation in Acute Myeloid Leukemia, Leukemia & Lymphoma, 7:sup1, 45-49, DOI: 10.3109/10428199209061564 To link to this article: http://dx.doi.org/10.3109/10428199209061564

Published online: 01 Jul 2009.

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Date: 11 November 2015, At: 13:10

0 1992 Harwood Academic Publishers GmbH

Leukemia and Lymphoma, Vol. I, Supplement, pp. 4 5 4 9

Printed in the United Kingdom

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Use of High-Dose Cytarabine in Autologous Bone Marrow Transdantation in Acute Myeloid Leukemia Downloaded by [Deakin University Library] at 13:10 11 November 2015

RUGGERO MOZZANA*, ALDO DELLA VOLPE*, CHIARA BUTTI*, VITTORIO FOSSATI?, SILVANA SELVAS, and GIORGIO LAMBERTENGHI DELILIERS* 'Institute of Medical Sciences, University of Milan, Italy. tlRCCS S. Raffaele, Milan, Italy. SIRCCS Ospedale Policlinico, Milan, Italy

Autologous bone marrow transplantation is widely used as late intensification therapy for patients with AML in remission without an HLA identical donor or who are older than 4 M 5 years. We report our experience in 21 AML patients in 1st or 2nd CR transplanted with a regimen including HD-ARA-C in addition to Cyclophosphamide (CY) and TBI. The median age was 32 years (3-50). Fourteen patients were transplanted in 1st CR and 7 in 2nd CR. In all but one patient BM harvesting and ABMT were done in the same remission status and after at least 3 courses of consolidation therapy. 15 and Day +31. Two patients (9.50/,) died from treatment related toxicity on Day The median time to reach 1000 WBC and 50000 platelets per cmm was 23 (13-55) and 55 (22-790) days respectively. Only 4 (21%) of the 19 evaluable patients (median observation time of 32 months) relapsed, at 3, 8, 18 and 26 months from ABMT. The projected event free survival curve shows survival of 67% at 96 months with a relapse rate of 26%.

+

KEY WORDS:

HD-ARA-C

autologous bone marrow transplantation

In acute myeloid leukemia (AML) complete remission (CR) is obtained in more than 70% of the adult patients on conventional therapy but, despite various strategies to maintain remission, the majority of patients relapse within 2 years. High dose chemotherapy with or without total body irradiation (TBI), followed by the reinfusion of previously harvested and cryopreserved bone marrow (BM), is widely used as late intensification therapy for patients with AML in remission without an HLA identical donor or who are older than 40-45 years; the survival rate ranges from 40% to 60%'-*. The

AML.

timing of transplantation, the type of pretransplant regimen and the real efficacy of the procedure are still open questions. In order to eliminate possible residual leukemic cells, several purging methods using drugs or antibodies before cryopreservation have been p r ~ p o s e d ~So - ~ far, . the results of prospective studies evaluating the efficacy of conventional therapy versus autologous and allogeneic BMT are few and preliminary l o * '. The efficacy of high-dose ARA-C (HD-ARA-C) in achieving remission in patients with refractory acute leukemia" suggested its use in a preparative regimen for AML patients submitted to ABMT. We report our experience in 21 AML patients in 1st or 2nd CR transplanted with a regimen Address for correspondence: Prof. Ruggero Mozzana, lstituto di Scienze Mediche, Pad. Granelli. Via F. Sforza 35, including HD-ARA-C in addition to Cyclophos20122 Milano, Italy. phamide (CY) and TBI. 45

46

R. MOZZANA, el a/.

Preparative regimen

MATERIALS AND METHODS

The first four patients were treated with ARA-C (2g/m2/12h) on Days -9, -8, CY (60 mg/kg/d) on Days -6, -5 and TBI (3.33 Gy/d-dose rate 3-4 cGy/min) on Days - 3, -2, - 1, followed by BM reinfusion on day 0. In the remaining 17 patients the dose of ARA-C was increased to 3 g/m2/12h.

Downloaded by [Deakin University Library] at 13:10 11 November 2015

Patients

Between September 1983 and June 1991, twenty one consecutive AML patients (M1 + M2 = 11, M3 = 5, M4 = 1, M5 = 4) were treated with ABMT in our Institution. Their median age was 32 years (3-50). Fourteen patients were transplanted in 1st CR and 7 in 2nd CR. In all but one patient, BM harvesting and Supportive care ABMT were done in the same remission status and after at least 3 courses of consolidation therapy. Patients were kept in a laminar flow room with a Before marrow harvesting the complete remission was central venous catheter placed for the administration confirmed by BM aspirate and biopsy. The median of chemotherapy, blood products and parenteral between the achievement of CR and ABMT was 7 nutrition. Decontamination of the gut was performed months (1-21). Patient data are listed in detail in by means of non absorbable antibiotics and antimycotics. When fever exceeded 38"C, empirical antibiotic Table 1. therapy was started and if the fever persisted for more than four days despite an adequate systemic antibiotic Marrow harvesting and processing therapy, systemic amphothericin B was given. Platelet BM was collected by multiple aspirations from the transfusions were given to mantain a platelet count posterior iliac crest. The technique of marrow over 20000/cmm. In order to avoid GVHD, all blood processing, cryopreservation and reinfusion have been products were irradiated with 20 Gy. No blood previously described". products screened for CMV were administered.

Table 1 Patients data PIS.

Age/sex (Yrsl

FAB

CR

Time CR-ABMT (months)

Outcome

V.T. C.R. M.G.C. N.C. C.M. D.V. C.F. D.C. B.M.L. F.C. G.R. A.F. D.M.G. L.R. C.A. A.V. I.C. F.V. B.E. A.R. A.C.

20/M 2l/M 11/M 26/M 11/M 3/M 34/F 49/F 38/F 36/M 28/M 26/F 42/M 50/M 26/M 32/M 40/F 28/M 46/F 48/F 48/F

M1 M2 MI M3 M5 M5 M1 M5 M1 M3 M3 M2 M1 M1 M5 M3 M3 M4 M1 M2 M2

2nd 2nd 2nd 1st 2nd 2nd 1st 1st 1st 1st

21 4 1' 1 6 6 10 13 12 1 10 9 1 6 12 8 8 6 7 6 9

A/W in CCR at 96 + m Dat 1 m R a t 3 m - D a t 11 m R at 18 rn - D at 19 m R a t 26 rn - D at 40 m A/W in CCR at 48 + rn A/W in CCR at 43 + m A/W in CCR at 43 + m A/W in CCR at 41 + m A/W in CCR at 36 + rn A/W in CCR at 36 + m A/W in CCR at 33 + m A/W in CCR at 32 + m A/W in CCR at 29 + rn Dat