efficacy of hematopoietic stem cell transplantation and prophylactic triple intrathecal therapy in a...
TRANSCRIPT
Letter to the Editor
Efficacy of hematopoietic stem cell transplantation and
prophylactic triple intrathecal therapy in a child with multiple
CNS relapse of acute lymphoblastic leukemia
Dear Editor,Most patients with isolated central nervous sys-
tem (CNS) relapse have good outcomes when trea-ted with intrathecal and systemic chemotherapyfollowed by irradiation to the neuroaxis. However,the role of hematopoietic stem cell transplantation(HSCT) and prophylactic intrathecal therapiesafter transplantation remains unclear for thosepatients with refractory or multiple CNS relapses(1, 2). Therefore, we want to emphasize that alloge-neic HSCT and prophylactic triple intrathecal ther-apies after HSCT could be useful treatmentoptions for children with multiple CNS relapse.The patient was initially diagnosed as B precur-
sor ALL without CNS involvement at the age ofthree yr and received St Jude Total XIII protocol.Until the age of nine yr, he had isolated CNSrelapse twice. When he was at nine yr of age, hewas diagnosed as third isolated CNS relapse of Bprecursor ALL. He received 1800 cGy cranialradiotherapy and 2200 cGy local radiotherapy tohis left eye. Remission was achieved within onemonth. HLA identical–related or unrelated donorcould not be found, and HSCT could not be per-formed until his third relapse. During this period,he had a new sister who is HLA identical with ourpatient. Thus, he underwent bone marrow trans-plantation (BMT) from his HLA identical sister.His conditioning regimen included 1200 cGy TBI(2x200cGy/day) at days �7, �6, �5 and etoposide(60 mg/kg) at day �3. He received 3.7 9 106/kgCD 34(+) stem cells and 4 9 108/kg nucleated cells.Neutrophil engraftment was achieved at day +16and platelet engraftment at day +23. Acute graftversus host disease (GvHD) prophylaxis comprisescyclosporine A (CsA) and short-term methotrexateat a dosage of 10 mg/m2 at days +1, +3, and +6. Hehad an uneventful post-transplant course, anddonor chimerism of 95% was achieved at +1month. However, his chimerism decreased to 67%
at third month. After third month of HSCT, CsAwas decreased and ceased at fifth month of trans-plantation to achieve a graft versus leukemia effect.In addition, prophylactic triple intrathecal treat-ments were started to prevent CNS relapse. Intra-thecal treatments were administered at one-monthintervals for the first six months and at two-monthintervals for the second six months. His chimerismstudies were 69% at sixth month, 60% at ninthmonth, 71% at 12th month, 72% at 15th month,and 70% at second year. He did not use any medi-cation for more than one yr. Now, he is in goodclinical condition and has been followed up in ourBMT unit for more than two yr after HSCT.
Allogeneic HSCT is an effective treatmentoption for early isolated CNS relapse (<18 months)or multiple CNS relapse. However, informationparticularly on the long-term outcome of trans-plant recipients is limited. Yoshihara et al.performed allogeneic HSCT in seven children withALL and one child with T-cell type non-Hodgkin’slymphoma having isolated CNS relapse. Allpatients survived for a median of 70.5 (range,13–153) months after HSCT. Except for a pre-school child with post-transplant CNS relapse, sixof seven children showed normal school/social per-formance. These results indicated a high cure rateof isolated CNS relapse by allogeneic HSCT inpediatric lymphoid malignancies. However, one ofeight children underwent HSCT had CNS relapseeven after transplantation (3). Our patient is a veryhigh risk patient for CNS relapse due to the multi-ple CNS relapses and having mixed chimerismafter transplantation. Therefore, he received post-HSCT intrathecal treatments for one yr. The effec-tiveness of post-transplant prophylactic intrathecaltreatment for such a high risk patient has not beentested, previously (1).
Hibi et al. (4) have evaluated donor–recipientchimerism on the CSF mononuclear cells in
E346
© 2013 John Wiley & Sons A/S.
Clin Transplant 2013: 27: E346–E347 DOI: 10.1111/ctr.12167
pediatric patients with ALL who were underwentsex-mismatch allogeneic HSCT with TBI contain-ing conditioning regimens by FISH using satelliteDNA probes for human X and Y chromosomes.They found that CSF cells showed complete donortype in 19–97 d after allogeneic HSCT, when com-plete donor type hematopoiesis was observed.They suggested that after children received TBIcontaining conditioning regimens, blood-brainbarrier becomes more permeable and leukocytesenter into the brain easily. The rapid entry of thedonor lymphocytes into the brain may show bene-ficial effects to eradicate the residual CNS leukemiccells and prevent a CNS relapse in children withALL after HSCT.
Our patient had CNS relapses at three timesbetween the ages of three and nine. During thesesix yr, he had chemotherapy, radiotherapy, andintrathecal therapies. However, he had still hadCNS relapses despite this intensive treatment strat-egy. After allogeneic HSCT and prophylactic tripleintrathecal treatments, he had no relapse for morethan two yr. Thus, this long period of no relapsesuggested that allogeneic HSCT and prophylactictriple intrathecal treatments are an effective treat-ment strategy in children with poor prognosis mul-tiple CNS relapse.
Betul Tavila, Ali Ayc�icekb, Fatih Azika, BahattinTunca, Buket Erer Del Castelloc, and Duygu
Uc�kanaaDepartment of Pediatric Hematology, AnkaraChildren’s Hematology and Oncology Hospital,Ankara, bDepartment of Pediatric Hematology,
Harran University Faculty of Medicine, Urfa andcDepartment of Pediatric Hematology, Ege Univer-
sity Faculty of Medicine, _Izmir, Turkeye-mail: [email protected]
References
1. PUI CH, HOWARD SC. Current management and challengesof malignant disease in the CNS in paediatric leukaemia.Lancet Oncol 2008: 9: 257.
2. PUI CH, THIEL E. Central nervous system disease in hema-tologic malignancies: historical perspective and practicalapplications. Semin Oncol 2009: 36: S2.
3. YOSHIHARA T, MORIMOTO A, KURODA H et al. Allogeneicstem cell transplantation in children with acute lymphoblas-tic leukemia after isolated central nervous system relapse:our experiences and review of the literature. Bone MarrowTransplant 2006: 37: 25.
4. HIBI S, TSUNAMOTO K, TODO S et al. Chimerism analysis onmononuclear cells in the CSF after allogeneic bone marrowtransplantation. Bone Marrow Transplant 1997: 20: 503.
E347
Letter to the Editor