AlloSCT In Children Research Articles

Physical and emotional well-being of survivors of childhood and young adult allo-SCT - A Danish national cohort study.

The aim of this investigation was to examine, within a population-based study of a national cohort comprising Danish survivors of allo-SCT (n = 148), the long-term effects of allo-SCT in children and young adults. Physical and emotional well-being was assessed using the Short Form 36 (SF-36) and the HADS. Allo-SCT-related data were obtained from the participants' medical records. The study includes 148 patients, with an 89% response rate (n = 132). For comparison purposes, norm data from Danish (1994, n = 6000), Swedish (2006, n = 285), and British (2001, n = 1792) population samples were used. Factors negatively influencing the SF-36 subscales included female gender; TBI; stem cells derived from PB; older age at time of questioning; and living alone. Factors significantly (p < 0.05) influencing HADS were transplantation with stem cells derived from PB and being underweight at time of questioning (median values were within normal range). Overall scores of allo-SCT patients were similar to norm data. In conclusion, this national cohort study shows that patients treated with SCT in early life (<25) and whose survival period extended beyond 10 yr (mean) from SCT, showed similar levels of anxiety, depression, and physical and emotional well-being to those of the normal population.

New frontiers in pediatric Allo-SCT.

The inaugural meeting of 'New Frontiers in Pediatric Allogeneic Stem Cell Transplantation' organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric Allo-SCT in children and adolescents with malignant and non-malignant disease (NMD), to share information and develop future collaborative strategies. The primary objectives of the conference included: (1) to present advances in Allo-SCT in pediatric ALL and novel pre and post-transplant immunotherapy; (2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; (3) to discuss timing of immune reconstitution after Allo-SCT and methods of facilitating more rapid recovery of immunity; (4) to identify strategies of utilizing Allo-SCT in pediatric myeloproliferative disorders; (5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric Allo-SCT; (6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and (7) to discuss optimizing drug therapy in pediatric recipients of Allo-SCT. This paper will provide a brief overview of the conference.

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.

Outcomes After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) In 163 Pediatric Patients (

IntroductionOutcomes after RIC allo-SCT in children are rarely reported. The largest series published thus far included 47 children with hematologic malignancies (Pulsipher et al, Blood, 2009). There is thus currently no large series describing the results of RIC allo-SCT in children. Patients and Methods163 pediatric patients (<18 years old, median age: 15.8 years (range: 2.9-17.9)) who received RIC allo-SCT for a hematologic malignancy were reported to the SFGM-TC registry between 1998 and 2011. Median year for transplant was 2005. The majority of cases had myeloid malignancies (59.5%) and most of the patients were in complete remission (CR) at transplant (65%, CR1 n=45; CR2 n=39, CR3 n=23, active disease n=40, missing data n=16). Forty-eight (29.5%) and 30 (18.5%) patients had received prior autologous SCT or allo-SCT, respectively. Donors were HLA-matched related in 48 cases; mismatched related n=5; MUD n=59; mismatch unrelated n=10. The source of stem cells was bone marrow, PBSC and cord blood in 44%, 31% and 25% of cases, respectively. ResultsEngraftment was observed in 85.5% of cases with a median time for neutrophils recovery of 20 days (range: 1-79). With a median follow-up of 23 months (range: 1-169), 2-year (2-y) OS, DFS, RI and NRM were 46+-5%, 37.5+-4%, 40+-3% and 22+-3%, respectively. Cumulative incidence (CI) of acute GVHD at day+100 was 36+-4% while 2-y CI of chronic GVHD was 24.5+-3%. In univariate analysis, factors such as disease status (CR vs active), donor type, source of stem cells, TBI or ATG administration were not associated with outcomes. There were a trend for better 2-y DFS in patients allotransplanted after 15.5 months from the diagnosis (42+-6% vs 33+-6%, p=0.09), for higher 2-y RI but a lower 2-y NRM in patients allografted before 10 years old (52+-7% vs 35+-5%, p=0.07; 12+-5% vs 35+-5%, p=0.06, respectively) and finally a trend for better 2-y OS in patients with lymphoid malignancies (54+-7 vs 41+-6%, p=0.09). Patients allografted after 2004 (n=122; median age: 13.2 years (range: 1-17.9); male 60%; myeloid malignancies 59%, CR: 63%) showed significantly higher 2-y OS (52+-5% vs 31+-7%, p=0.006) and DFS (45+-5% vs 18+-6%) due in part to a significantly lower 2-y NRM (17+-4% vs 36+-8%, p=0.01) reflecting probably a better patient's selection before transplant. In patients allografted since 2004 multivariate analysis revealed that lymphoid malignancy was the only favourable and independent factor for LFS and OS (HR: 0.55, 95%CI: 0.32-0.97, p=0,04; HR: 0.47, 95%CI: 0.25-0.88, p=0.02). ConclusionThis large series shows that RIC allo-SCT is feasible with acceptable toxicity in pediatric patients, especially in cases of lymphoid malignancy. Prospective studies are needed to confirm the potential role of RIC allo-SCT in the pediatric setting, with a special focus on long-term side effects, which are a matter of concern in children. Disclosures:Mohty:Novartis: Honoraria, Research Support Other.

A Phase I Study of Gemtuzumab Ozogamicin in Combination With a Myeloablative Conditioning (MAC) Regimen and alloSCT in Children With High-Risk CD33+ AML: A New Targeted Immunochemotherapy Conditioning Regimen (GO-BU/CY)

A Phase I Study of Gemtuzumab Ozogamicin in Combination With a Myeloablative Conditioning (MAC) Regimen and alloSCT in Children With High-Risk CD33+ AML: A New Targeted Immunochemotherapy Conditioning Regimen (GO-BU/CY)

Treatment of Pediatric Chronic Myeloid Leukemia in the Year 2010: Use of Tyrosine Kinase Inhibitors and Stem-Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the only proven cure for chronic myeloid leukemia (CML), a rare malignancy in childhood. With the excellent results induced by the tyrosine kinase inhibitor (TKI) imatinib in adults in the last decade, the appropriate management of children with CML has also changed radically, and only a minority are now transplanted as a front-line treatment. Data on pediatric experiences with imatinib in CML from controlled trials remain very limited, but this review of available data describes the role of imatinib in children with CML, addressing: 1) the starting dose; 2) pharmacokinetics in childhood; 3) possible adverse effects, with a focus on the still-growing skeleton; 4) early monitoring of treatment efficacy in an attempt to avoid failure; 5) the timing of allo-SCT in children; and 6) treatment of CML relapse after allo-SCT. Because the characteristics of CML in children seem to overlap extensively with what is described in adult internal medicine, most answers and pediatric algorithms are adapted from the treatment of CML in adults. Today in 2010, allo-SCT in children should be postponed until CML becomes refractory to imatinib. The approach for young patients with suboptimal responses is unclear because data on the efficacy and safety of second-generation TKIs in childhood are almost entirely missing. Other than being included in a formal trial on second-generation TKIs, allo-SCT for patients failing imatinib remains the first choice.

Significant Reduction of Treatment Related Mortality after Stem Cell Transplantation in 647 Children and Adolescents with ALL within BFM Trials during the Last 12 Years: A Long Term Analysis from 1996 to 2007

Although allogeneic stem cell transplantation (alloSCT) effectively prevents relapse of acute lymphoblastic leukemia (ALL), transplant related mortality (TRM) associated with the procedure may counterbalance that beneficial effect. To asses the risk for TRM after alloSCT we analyzed the different transplantation outcome data within the Berlin-Frankfurt-Münster (BFM)-trials. Between January 1996 and December 2003 403 patients were transplanted within ALL-BFM and ALL-Rez BFM trials (185 in CR1, 218 in CR2 or after subsequent relapse). These chemotherapy protocols included recommendations for alloSCT, however donor selection, conditioning regimen and GvHD prophylaxis frequently were modified by transplant centers. In 2003 the BFM Study Group initiated a prospective international multicenter trial (ALL-SCT-BFM 2003) aiming to standardize and harmonize the SCT procedure in order to minimize risk of TRM. Between January 2004 and December 2007 244 patients (109 in CR1, 135 in CR2 or after subsequent relapse) were recruited by 27 participating SCT centers in Austria, Germany and Switzerland. Indications for SCT were poor response to induction treatment, either detected by morphology on day 33 (NRd33) or by minimal residual disease load measured after 12 weeks of treatment, cytogenetic aberrations [t(9;22), t(4;11)], early bone marrow relapses of ALL, or any subsequent ALL relapse. More than 80% of all patients who were enrolled in ALL-SCT-BFM 2003 received the recommended conditioning regimens and GVHD prophylaxis (TBI+VP16 for MSD, TBI+VP16+ATG for MD, and TBI+Flu+VP16+ATG for MMD; in children younger than 2 years, TBI was substituted by BU+Cy; CSA in MSD-SCT, CSA plus short MTX in MD-SCT). Patients of both time periods (1996 to 2003 vs 2004 to 2007) were comparable regarding gender, immunophenotype, cytogenetic aberrations, NRd33 and type/time of relapse (if SCT in CR2). However, in the second time period there was a trend to older age at diagnosis (54.5% vs. 43.9% patients older than 10 years). Moreover, unrelated donors were used more frequently over time (61.9% vs 50.1%). Nevertheless TRM was significantly lower within ALL-SCT-BFM 2003 (11.5% vs 19.9%; p(Chi-Square)=0.006). In a logistic regression analysis including age above 10 and donor other than matched related as covariables the p-value was 0.001. TRM reduction over time was observed in MSD transplants (n=229) from 13.6% to 6.7% (p(Chi-Square)=0.12), in unrelated donor SCT (n=353) and mismatched related donor SCT (n=65) TRM decreased from 23.7% to 13.6% (p(Chi-Square)=0.01). Despite a trend to higher age at diagnosis and a higher percentage of unrelated donor transplantations, TRM reduced significantly since start of ALL-BFM SCT 2003. The experience of participating centers as well as high compliance to the recommended regimen, improved donor selection by HLA-high resolution typing, better diagnostic measures and (preemtive) treatment of infections, and close and prospective monitoring of all patients may contribute to the reduced TRM after alloSCT in children with ALL.

Allo-SCT in children with high-risk leukemia using unmanipulated grafts from alternative donors

Allogeneic HSCT is a curative treatment for high-risk leukemia. In Europe, approximately 15% of children have an HLA-matched sibling, but in 65-70% HLA allele-matched (9-10/10) unrelated donors (UD) can be identified. Transplantation using an HLA partially mismatched donor, unrelated cord blood or haploidentical family donor with graft manipulation is then considered with preference on the basis of local experience and/or availability. Here we evaluate the outcomes of 87 consecutive patients with leukemia transplanted with unmanipulated graft from matched or partially mismatched UD or cord blood (CB) at our institution between January 2001 and December 2007. Within the median follow-up of 30 months, the acute GVHD grade II was diagnosed in 70.9% patients; grades III-IV only in 4.6%. The overall incidence of chronic GVHD was 43.3% (extensive in 34.9%). The probability of 3-year EFS was 59.5% and that of 3-year overall survival was 66.9%. TRM at day +100 was 4.5%, and overall it was 13.8%. Fourteen patients (16.1%) died as a consequence of post-transplant leukemia relapse. We conclude that the prognosis of patients transplanted for leukemia using unmanipulated grafts from HLA-matched or partially mismatched UD or CB is comparable and satisfactory. TRM and relapse rate are lower than in the earlier period.

Preliminary results of gemtuzumab ozogamicin (GO) during myeloablative conditioning for allogeneic stem cell transplantation (AlloSCT) or following reduced intensity alloSCT (RI-AlloSCT) in children with AML

7038 Background: CD33 is expressed in 80–90% of childhood AML. GO, an immunotoxin targeting CD33, induces remission in 20–30% of relapsed/refractory childhood AML. Standard myeloablative conditioning (MAC) for AlloSCT in children with standard risk AML (SR-AML) is BU/CY. However, this regimen may be associated with 32% transplant related mortality (TRM) and 25% risk of relapse in SR-AML (Woods et al, Blood, 2001). Outcome following AlloSCT for high risk (HR) AML (≥CR3, induction failure [IF], refractory disease) is dismal (≤10% OS). There is a need for novel therapy during conditioning and after AlloSCT that can reduce TRM and relapse in SR-AML and improve outcome in HR-AML. Methods: We have performed 2 phase I studies of GO. In the first study of CD33+ HR-AML GO was dose escalated on day - 14 (3–7.5 mg/m2) prior to BU /CY MAC regimen. In the 2nd study of CD33+ SR-AML 2 doses of GO (4.5- 9 mg/m2) were administered ≥60d post reduced intensity conditioning (RIC) AlloSCT (8 wks apart). Results: In the HR-AML study, ten pts (2 CR3, 5 IF, 3 refractory) were studied. One pt died of chronic GVHD, 4 died of progressive disease, and 5 remain alive with no evidence of disease (NED). One pt developed mild VOD that resolved without therapy. In the SR-AML study, 11 pts, (8-CR1 and 3-CR2), received BU/FLU RIC. Nine pts received two doses of GO (Table) at mean d+78 and +153, respectively. One pt received one dose of GO but relapsed and died. One pt had primary graft failure. Nine pts are alive with NED; 1pt died from cGVHD. There has been no DLT secondary to GO and the MTD of GO in each study has not been reached. Conclusion: GO has been safe and well tolerated either added to MAC in children with HR-AML or as consolidation following RI-AlloSCT in SR-AML. We are currently accruing patients at the final dose level of GO in both studies. Study Conditioning GO Dose Median Age(range) Donors Myeloid Recovery (days) ANC>500/mm3× 2 days Platelet Recovery (days)(> 20,000/mm3 × 7 days UNTX) Mean Donor ChimerismDay-30 HR-AML Myeloablative 3mg/m2 [n=3] 8 yr 1 6/6 HLA-MSD, 24±10 54±49 96%±5 BU:12.8–16mg/kg 4.5mg/m2[n=3] (0.75-17) 1 10/10 MUD CY:120 mg/kg± ATG 6mg/m2 [n=3] 8 UCB (3 6/6, 2 5/6 and 3 4/6) 7.5mg/m2[n=1] SR-AML Reduced Intensity 4.5mg/m2[n=3], 11 years 8 6/6 HLA-MSD 15±4 16±16 97±2% BU:6.4–8mg/kg 6mg/m2 [n=4], (0.5-21) 1 5/6 MRD FLU: 150mg/kg ± ATG 7.5mg/m2 [n=3] 2 4/6 UCB. No significant financial relationships to disclose.

Improvement in Hemolytic Parameters and Tricuspid Regurgitant Jet Velocity (TRV) Following Non-Myeloablative Allogeneic Stem Cell Transplantation (allo-SCT) in Adults with Severe Sickle Cell Disease (SCD).

Although SCD has a variable clinical course, many individuals develop end-organ complications that are associated with significant morbidity and early mortality. SCD-related pulmonary hypertension is a frequently recognized complication (up to 30%), is associated with significant mortality, and is resistant to hydroxyurea or chronic exchange transfusions. Currently myeloablative allo-SCT in children under age 16 is curative in the majority, preventing or ameliorating many of the complications of the disease. However, it is unclear whether reduced intensity allo-SCT in adults that allows mixed hematopoietic chimerism could offer the same benefit. Furthermore, reversal of pulmonary hypertension has not been previously demonstrated in either setting. Beginning in 2003, we initiated an IRB approved clinical trial testing a nonmyeloablative approach in adults with severe SCD. Protocol entry criteria include end-organ complications, (stroke, pulmonary hypertension TRV≥ 2.5 m/s, or frequent vaso-occlusive crises or acute chest syndrome not ameliorated by hydroxyurea. Conditioning was achieved with low dose radiation, alemtuzumab, and sirolimus (rapamycin). All patients receive unmanipulated G-CSF mobilized peripheral blood progenitors obtained from an HLA-matched sibling. Assessment of donor chimerism is measured by microsatellite PCR of CD3 and CD14/15 positive white cells. Hemolysis is monitored by serial measurements of total bilirubin, lactate dehydrogenase, hemoglobin and absolute reticulocyte counts. Transthoracic echocardiography is performed in all patients, and serially in those with TRV ≥ 2.5 m/s. Transmitral flow, Doppler determinations of valvular regurgitant velocity, and left ventricular stroke volume are assessed and graded. A total of 8 patients have accrued. 4 of 8 patients met criteria for pulmonary hypertension. Post transplant follow-up for these 4 patients ranged from 7 to 36 months and stable donor lymphoid (13–39%) and myeloid (53–100%) chimerism was observed in all 4. This pattern of mixed chimerism was sufficient for full donor erythroid engraftment as all demonstrated normal hemoglobin, allowing for therapeutic phlebotomy to correct transfusional iron overload. Improvement in TRV and hemolytic parameters were observed (see table) as early as 3 months post transplant. The average pre- and post allo-SCT values were: TRV 3.1 → 2.5 m/s (p=0.13, Wilcoxon rank sum), total bilirubin 4.0 → 0.6 (p=0.1), lactate dehydrogenase 487 →178 units/L (p=0.2), hemoglobin (hgb) 8.6 → 12.6 g/dL (p=0.002), and reticulocyte (retic) count 326 → 68 k/uL (p=0.01). Our results indicate that reduced intensity allo-SCT in adults patients with SCD allows for full donor erythroid engraftment, normalization of blood counts, reversal of hemolysis, and improvement in TRV.TRV and hemolytic parametersPatient 1Patient 2Patient 3Patient 4AverageTRVPre3.72.63.42.63.08(m/s)BMT2.62.42.52.32.45T biliPre8.34.01.91.94.0(0.1–1.1 mg/dL)BMT0.80.50.50.40.6LDHPre1065330338215487113–226 units/L)BMT23417820990178HgbPre8.18.58.88.98.6(g/dL)BMT12.913.911.911.612.6ReticPre344213417331326(31–105 k/uL)BMT7632768768

A pilot study of myeloablative (MA) autologous stem Cell (Auto SCT) followed by reduced intensity (RI) allogeneic transplantation (AlloSCT) in children with relapsed/refractory(R/R) Hodgkin’s disease (HD)

20007 Background: Allo SCT may benefit patients with R/R HD by providing a graft vs lymphoma effect. Peggs et al (Lancet 2005) demonstrated durable engraftment and reduced non relapse mortality (NRM) in HD pts post RI Allo SCT. Carella et al (JCO2000) and Gutman et al (BMT2005) demonstrated the success of MA Auto SCT followed by RI AlloSCT in adults with refractory lymphoma. We investigated the feasibility of MA Auto SCT followed by RI Allo SCT in children with R/R HD. Methods: MA conditioning prior to AutoSCT was CTX 1,500 mg/m2 x 4 d, BCNU 100 mg/m2 x 3d, VP-16 800 mg/m2 x 3d. AlloSCT conditioning was fludarabine 30 mg/m2 x 5d, busulfan 3.2 mg/kg x 2d, and R ATG 2 mg/kg x 4d (unrel. donor). CD20+ patients received rituximab (375 mg/m2/wk x4) and all pts received involved field radiotherapy (IFRT). Results: Ten pts have enrolled, 2 pts did not proceed (parental withdrawal) to RI AlloSCT (Donors: 1 MRD, 2 MUD, 5 UCB). Median time to RI AlloSCT after MA Auto SCT was 142 d (97–219). The median cell dose was 3.43 x 107 TNC/kg for UCB grafts (n=5). Engraftment was achieved at a median of 20.5 d for PMN and 46.5 d for PLT. Donor chimerism reached ≥ 95% in all pts by day 100 with a median follow up of 703d (128–2025). Toxicities were grade (3) hematuria (n=1), (3–4) infection (n=7), (4) pulmonary fibrosis (n=1), (4) hearing loss (n=1), (4) neurotoxicity (n=1). GVHD: grade II-III aGVHD (3/8), cGVHD (3/8). Six patients are alive and NED post allo SCT. There has been one NRM (cGVHD) and one relapse mortality. The OS at one year is 66.7%. Conclusions: MA AutoSCT followed by RI AlloSCT is feasible and well tolerated in pediatric pts with R/R HD. A larger study with longer follow up is required to determine if this approach will reduce relapse, long term toxicity and/or improve survival. No significant financial relationships to disclose.

Targeted immunotherapy with gemtuzumab ozogamicin (GO) following reduced intensity allogeneic stem cell transplantation (RI AlloSCT) to reduce minimal residual disease (MRD) in children with acute myeloid leukemia (AML): MRD monitoring by Wilms tumor gene

9532 Background: RI vs myeloablative (MA) AlloSCT in adults with AML is associated with significantly less transplant related mortality but increased rate of relapse, presumably secondary to MRD (Alyea et al; Blood, 2005). Quantification of the WT1 has been used successfully to detect MRD in children with acute myeloid leukemia (AML) (Kletzel et al; Pediatr Dev Pathol, 2002). GO has induced ORR in &gt;30% of patients with overt relapsed CD33+ AML and may have a better effect in the setting of MRD (Sievers et al; J Clin Oncol, 2001). We have shown that RI AlloSCT followed by 2 doses of GO in average risk AML has resulted in &gt;94% donor chimerism (Roman/Cairo, Clin Can Res, 2005). We explored changes in MRD prior to and after consolidation with 2 doses of GO targeted immunotherapy in children with average risk AML post RI AlloSCT. Methods: 11 pts, 11 years (0.5–21) with CD33+ (8 CR1, 3 CR2) received fludarabine 30 mg/m2x6d and busulfan 3.2–4 mg/kgx2d. Donors: 7 6/6 HLA related peripheral blood stem cells (RPBSC), 1 5/6 RPBSC, 1 6/6 related cord blood (CB) and 2 4/6 unrelated CB. GOx2 was administered =60d post AlloSCTx2 (8wks apart), at 4.5–7.5 mg/m2 (dose escalation). Samples were collected for WT1 analysis prior to and after each dose of GO (n=5). WT1 levels were determined by quantitative RT-PCR and compared with WT1 expression in a K562 leukemia line. Positive MRD was a ratio of K562 WT/patient's WT1&gt;0.5. Results: The MTD for GO post RI AlloSCT has not been reached. 8/11 are NED (3 deaths: 1 relapse, 1 graft failure, 1 cGVHD) Pre GO WT1–0.079±0.07 (n=5), pre GO-dose #2–0.012±0.016 (n=3). One of these patients had detectable MRD (WT1–1.56) prior to the GO-dose #2, no MRD at 1year and is alive and in remission at 2 years post GOx2. The fifth patient entered transplant with +MRD (WT-0.866), relapsed after the first dose of GO and died of relapse prior to receiving the second dose. Conclusions: Targeted therapy with GOx2 may be useful in eradicating MRD in patients post RI AlloSCT. A larger cohort is necessary to assess the impact of GO (at the MTD) on MRD post RI AlloSCT in children with AML. No significant financial relationships to disclose.

A pilot study of myeloablative (MA) autologous stem cell (autoSCT) followed by reduced intensity (RI) allogeneic transplantation (AlloSCT) in children and adolescents with relapsed hodgkin’s disease (HD) and non-hodgkin’s lymphoma (NHL)

AlloSCT may be beneficial to patients with relapsed/refractory HD and NHL by providing a graft versus lymphoma effect. Carella et al (JCO 2000) and Gutman et al (BMT 2005) demonstrated the feasibility and success of MA AutoSCT followed by RI AlloSCT in adults with refractory lymphoma. We investigated MA AutoSCT followed by RI AlloSCT in children with relapsed/refractory HD/NHL. Twelve patients entered post reinduction therapy (3CR+2PR post Ifos/Carbo/VP-16, 1PR+1CR post Ifos/Vinorelbine, 1PR post Topotecan/Ifos/Carbo, 1CR post vinorelbine/gemcitabine, 1PR post cytarabine/VP-16/MTX, 1PR post cytarabine/VP-16/L-asp/prednisone, 1CR post carmustine/VP-16/cyclophosphamide).

A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients.

Reduced intensity (RI) allogeneic stem cell transplantation (AlloSCT) was initially demonstrated in adults following HLA-matched family and unrelated adult donor AlloSCT. There is little information about RI AlloSCT in children. We report results of a pilot study of RI AlloSCT in 21 recipients (< or =21 years). Age: median 13 (0.5-21) years, 8F:13M, 14 unrelated cord blood units (UCB) (10 4/6, 4 5/6), two related BM (6/6, 5/6), four related PBSC (2 6/6, 2 5/6), and one related BM+PBSC (6/6). RI: fludarabine, busulfan (n=14); fludarabine, cyclophosphamide (n=4); fludarabine, melphalan (n=1); total body irradiation, fludarabine, cyclophosphamide (n=1); or fludarabine, cyclophosphamide, and etoposide (n=1). Graft-versus-host disease prophylaxis: FK506 0.03 mg/kg/day and mycophenolate mofetil 15 mg/kg/q 12 h. UCB median nuc/kg and CD34/kg was 4.3 x 10(7)/kg (0.9-10.8) and 1.9 x 10(5)/kg (0.3-6.9), and related BM/PBSC median nuc/kg and CD34/kg was 8.3 x 10(8) (4.7-18.9) and 5.0 x 10(6)/kg (4.6-6.4). Maximal chimerism following unrelated cord blood transplantation, 100% x 7, 98% x 1, 95% x 2, 55% x 1, and 0% x 3; related PBSC/BM, 100% x 5, 65% x 1, and 55% x 1. Graft failure occurred in 5/21 (24%). In summary, RI AlloSCT in children is feasible and tolerable (< or =25% GF) and results in > or =85% of recipients initially achieving > or =50% donor chimerism.