Outcome of allogeneic stem cell transplantation with a conditioning regimen of busulfan, cyclophosphamide and low-dose etoposide for children with myelodysplastic syndrome

BACKGROUND AND OBJECTIVESAllogeneic stem cell transplantation (SCT) offers the best chance of cure and long-term survival for children with myelodysplastic syndromes (MDS).DESIGN AND SETTINGRetrospective analysis of pediatric patients with primary MDS treated with allogeneic SCT at a single institution treated between January 1993 and December 2008.PATIENTS AND METHODSOf 16 consecutive children who received allogeneic SCT for treatment of MDS in our center, 14 patients met the criteria of MDS according WHO I and II criteria. The median age was 4.8years (range, 1-14 years) and 64% were male. The median time from diagnosis to transplant was 6 months. MDS stage was refractory cytopenia (RC) in 9, refractory anemia with excess blasts (RAEB) in 5. Monosomy 7 was present in 35% of the patients. The majority of patients (11/14) were conditioned with a busulfan-based myeloablative (MA) regimen with addition of low-dose of etoposide (30mg/kg). All but one received a bone marrow graft.RESULTSNine patients achieved complete remission (CR), and seven remain alive. At a median follow-up of 3 years (range, 2-14 years) the OS and EFS was 57% (95%CI, 0.28-0.78). Cumulative EFS at 1 0 years was 43% (95% CI: 0.14-0.70). Relapse-related mortality was 21.4%; nonrelapse mortality (NRM) was 28.57%. All the survivors had etoposide in their conditioning regimen. Patients younger than 1 0 years had better survival (P=.001).CONCLUSIONChildren with MDS achieve encouraging OS and EFS following allogeneic SCT. A busulfan-based regimen with a lower dose of etoposide is an effective and less toxic regimen. The outcomes are best in younger patients

Outcomes of Unmanipulated Haploidentical Transplantation Using Post-Transplant Cyclophosphamide (PT-Cy) in Pediatric Patients With Acute Lymphoblastic Leukemia

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival

Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies

Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%; P = .006), well-matched (80 preCBT, 50% remained stable, 20% declined to 60 to 80, and 30% to, 60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes

Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia

Patients with chronic myeloid leukemia (CML) infrequently present in blast crisis (BC). While most BC are of myeloid origin, megakaryocytic BC is rare, especially at the time of CML diagnosis. We describe the first pediatric patient presenting with megakaryocytic leukemia and having BCR-ABL1 translocation as the single chromosomal abnormality. Clinical features were more suggestive of CML in megakaryocytic blast crisis than Philadelphia chromosome positive de novo AML. The patient was treated with AML-directed chemotherapy and imatinib mesylate followed by umbilical cord blood stem cell transplantation. The patient was in complete molecular response 16 months after stem cell transplantation

Outcome Of hematopoietic cell transplantation (HCT) In pediatric patients with Hodgkin lymphoma (HL): Single institution results from Saudi Arabia

Most pediatric patients with Hodgkin lymphoma are cured of their disease with standard combined-modality first-line therapy. Those who relapse are subjected to salvage chemo-radiotherapy, and patients who respond often undergo either autologous or allogeneic HCT, with a reported outcome ranging from 40%-60%. Variables affecting the outcome of such patients are not clearly defined. This study retrospectively reviewed the clinical characteristics and outcome of patients who underwent HCT at our institution. Between 1995 and 2012, 29 pediatric (age \u3c14 years) patients with HL underwent HCT. This cohort included 24 boys and 5 girls. Their median ages at initial diagnosis and at HCT were 9.85 years (mean 8.85; range 3.6-13.75) and 12.18 years (mean 11.24; range 5.6-14.9), respectively. 28 patients had classic HL (23 nodular sclerosis, 3 mixed cellularity, 1 lymphocyte-depleted, and 1 lymphocyte-rich) and one patient had nodular lymphocyte-predominance HL. Ten had persistent/progressive disease following first line therapy, while 19 had relapsed following achievement of complete response (CR). For these patients median time to relapse from completion of first-line therapy was 16.9 months (mean 20.1; range 1.9-53.1). All patients received salvage chemotherapy and/or radiotherapy prior to HCT; fifteen patients achieved CR, 13 had a partial response and one had progressive disease. Two patients had allogeneic bone marrow (BM) grafts from matched-related donors, while the rest had autologous grafts (16 BM; 10 PBSC; 1 BM+PBSC) following chemotherapy-based myeloablative conditioning. Twelve patients have relapsed/progressed post-HCT at a median of 6.04 months (mean 11.8; range 1.02-71.4). Nine patients have died; eight because of disease progression and one due to sepsis post HCT. Only two patients died within the first 100 days post HCT, giving a Day-100 mortality rate of 6.8%. Two patients who relapsed after HCT were salvaged with chemo/radiotherapy and remain disease free 2.8 and 9.7 years later. The 5-year estimated overall survival (OS) from HCT for the whole cohort is 61.6%, with an event free survival (EFS) of 57.9%. Patients who had persistent/progressive disease at the end first-line therapy or relapsed \u3c6months off therapy had a worse OS and EFS as compared to those who relapsed later (OS 42.9% v. 75.3%, p=0.047 [Taron-Ware]; EFS 41.7% v. 60.8%, p=0.052 [Taron-Ware]). The outcome of patients with relapsed/refractory HL following HCT is encouraging, as a majority of patients survive free of their lymphoma. Timing of relapse/progression remains an important prognostic factor and patients who fail early may be considered for novel therapeutic approaches

PN016 Outcome of allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia

Purpose: Juvenile myelomonocytic Leukemia (JMML) is a rare childhood Leukemia for which allogeneic stem cell transplantation (ASCT) is the only curative therapy. Early relapse remains the single most important obstacle to successful use of this treatment modality. We report here the outcome of ASCT in 18 pediatric JMML patients treated in our institution.Method: Eighteen consecutive patients (12 boys, 6 girls) with JMML underwent ASCT at our institution between Jan 1995 and Nov 2010. Prior to transplant, all patients but one were treated with chemotherapy. Splenectomy had been performed in 3 patients. At transplant, the disease was progressive, stable or in complete remission in 1, 13 and 4 patients, respectively. The median time to transplantation was 5.5 months (range: 2.5–15.3). The grafts were related marrows in 11 patients (HLA-identical relative in 10 patients and one-antigen mismatched in one) or partially matched unrelated cord in 7 patients (one-antigen mismatched in 2 and two-antigen mismatched in 5 patients). The conditioning regimen consisted of busulfan, cyclophosphamide and Etoposide in 12 and of busulfan and cyclophosphamide in 6 patients.Results: Four patients relapsed at a median time of 2.6 months (range: 1.4–7.8) post-transplantation, and subsequently died of progressive disease. All relapses occurred in children older than one year at presentation. One patient died of severe veno-occlusive disease and 2 patients died of septic shock at 14, 8 and 33 days post transplantation, respectively. The 5-year overall and event-free survivals of the whole group were 60% with a median follow up of the surviving patients being 74.5 months (range: 8.6–165).Conclusion: ASCT has dramatically improved survival of children with JMML. Age older than one year at presentation may predict an increased risk of disease recurrence however this merits a prospective evaluation in a larger cohort of patients

Outcome Of hematopoietic cell transplantation (HCT) in pediatric patients with non-Hodgkin lymphoma (NHL): Single institution results from Saudi Arabia

Although HCT is an accepted component of the treatment strategy for relapsed/refractory pediatric NHL, only few studies have reported on the outcome for these patients. Most have reported on small numbers of patients, with survivals ranging from 27% to 75%. Clinical data were retrospectively retrieved for patients with NHL who had undergone HCT. Pre-HCT information, including pathologic diagnosis, response to first- and second-line therapy and pre-HCT disease status were collected, in addition to details of the transplant process and patient and disease outcome. Between 1996 and 2012, 28 pediatric patients with NHL underwent HCT. Primary diagnosis for these patients included Burkitt lymphoma (n=13), Large B-cell lymphoma (n=4), T-Lymphoblastic lymphoma (n=4), NK/T cell lymphoma/leukemia (n=3), Peripheral T-cell lymphoma (n=2), B-lymphoblastic lymphoma ((n=1) and anaplastic large cell lymphoma (n=1). The median age at HCT was 7.65 years (mean 8.2; range 1-14.3). Twenty had suffered a relapse of their disease, while five had primary progression; three patients with NK/T lymphomas underwent HCT as part of their first-line therapy. Fourteen patients had autologous (autoHCT) and 14 had allogeneic HCT (alloHCT). Among alloHCT, 11 had matched-related grafts while 3 had unrelated umbilical cord blood (UCB) grafts. At the time of HCT, 23 patients were in CR (CR1=7, CR2=15, CR3=1), and 5 had partial responses. HCT conditioning was myeloablative for all patients; in 18 patients, it was TBI-based. Fourteen patients suffered recurrence of their lymphoma post HCT at a median of 1.17 months from HCT (mean 6.2; range 0.63-42); 4 died in CR due to transplant-related toxicity, of these 3 were post alloHCT and one post autoHCT. Three patients have developed secondary malignancies (SMN; 2 post alloHCT and 1 post autoHCT). 10 patients were alive at last follow-up, all of whom were in CR. The 5-year estimated OS from SCT is 38.7%, with and EFS of 26%. There was no difference in 5-year OS or EFS among patients who received alloHCT v. autoHCT (OS 28.6% v. 49%; p=0.53, EFS 14.3% v. 37.5%; p=0.25) and among patients who did or did not receive TBI (OS 33.3% v. 48%; p=0.37, EFS 27.8% v. 18.8%; p=0.66). OS/EFS for patients with Burkitt lymphoma was 23.1%. Of the three patients with NK/T cell lymphoma two remain alive in CR 13.7 and 5.1 years after HCT. The outcome of relapsed/refractory non-Hodgkin lymphoma of childhood remains suboptimal. In addition to a high post-HCT relapse rate of 50%, HCT-related toxic mortality and SMN contribute to the poor outcome for this cohort of patients

Outcome of risk adapted therapy for relapsed/refractory acute lymphoblastic leukemia in children

Results of second-line therapy for childhood acute lymphoblastic leukemia (ALL) remain suboptimal, particularly for high-risk groups identified using timing and site of relapse. We report results of prospectively collected data for pediatric patients with ALL who received risk adjusted second-line therapy. The 59 patients who failed first-line ALL therapy included 36 (61%) with bone marrow (BM), 13 (22.1%) with isolated extramedullary (EM) and 10 (16.9%) with BM + EM relapse. Some 51.8% patients were reinduced with high dose cytosine arabinoside (HDAraC)-based and 48.2% with standard four-drug regimens. In all, 38/56 (67.9%) achieved a complete remission (CR) with second-line therapy; the overall CR rate was 78.6% and was not associated with CR1 duration (p =0.8). Three-year overall survival (OS) was 45.3%, and was 61.4% for those achieving a CR. No risk group benefited from HSCT over chemotherapy. Patients with isolated EM relapse beyond 18 months of CR1 and BM relapse beyond 12 months off-therapy had an excellent outcome (OS 91.7%), identifying a particularly good-risk cohort. Patients not in this category continue with poor outcome even following hematopoietic stem cell transplant