Outcome of 46 children with refractory leukemia treated with unrelated donor hematopoietic stem cell transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of matched unrelated donor hematopoietic stem cell transplantation (UDT) and influencing factors in children with refractory leukemia.</p><p><b>METHOD</b>Retrospective analysis was performed on clinical data of 46 consecutive children received UDT between Nov. 2002 and Dec. 2008. A 12-14 GY fractioned total body irradiation (TBI) was given to children with acute lymphoblastic leukemia (ALL). Busulphan based myeloablative regimen was applied to all the other patients. ATG (Fresenius) 15 - 20 mg/kg + low dose cyclosporine A oral [CSA, 8 - 12 mg/(kg * d) with serum trough levels 150 - 200 ng/ml] +/- methotrexate (without methotrexate for cord blood transplant) were administered as graft versus host disease (GVHD) prophylaxis. Mycophenolate mofetil [MMF, 20 - 30 mg/(kg * d)] was added for 13 CML after Jan 1, 2006 because of more severe GVHD was observed in this group.</p><p><b>RESULTS</b>The median age was 8.0 (2 - 17) years with the median follow up period of 23.5 (0.7 - 85) months. The estimated 3 years overall survival (OS) was 63.0%; 23.9% patients died of transplant related mortality, 13.0% patients died of leukemia relapse. Cytomegalovirus (CMV) infection recurred in 50% patients and hemorrhagic cystitis in 15.2% patients; 33.3% patients developed grade III-IV acute GVHD and 55.6% developed chronic GVHD (13.9% with extensive chronic GVHD). The OS was significantly different between the patients older (n = 20) and younger (n = 26) than 10 years (45.0% vs. 76.9%, P = 0.015) and among the patients with ALL (n = 13), CML (n = 18) and AML (n = 15) (38.4%, 66.7% vs.80.0%, P = 0.034). The OS in patient with high risk leukemia (n = 24) was lower than that in the patient with low risk leukemia (n = 22) (45.8% vs. 81.8%, P = 0.012). Except 8 cord blood transplant the OS of patients with HLA 6/6 high resolution completely matched (n = 16) and 1/6 mismatched (n = 16) bone marrow and peripheral blood stem cell transplants was significantly higher than patients with 2/6 mismatched (n = 6) UDT (75.0%, 75.0% vs. 16.7%, P = 0.007). But the OS was not significantly different between patients with grade 0-II acute GVHD and III-IV acute GVHD (60.0% vs. 66.7%, P = 0.494).</p><p><b>CONCLUSION</b>The outcome of UDT for Chinese children with refractory leukemia is encouraging. Patients younger than 10 years with 0-1/6 high resolution mismatched UDT had the best OS. The outcome of patients with myeloid and low risk leukemia is superior to those with other types of leukemia.</p>

Clinical report on diagnosis and treatment of 14 cases with pediatric Ewing's sarcoma family tumors / 中华儿科杂志

<p><b>OBJECTIVE</b>To recognize and improve the outcome of childhood Ewing's sarcoma family tumors, and to identify the efficacy and safety of the chemotherapy using RS-2002 Protocol.</p><p><b>METHODS</b>From September 1997 to September 2006, 14 newly diagnosed patients with the tumors were admitted, 9 were boys, and 5 were girls, the median age was 7.04 years, ranging from 1.58 years to 11.67 years. Among them, 9 patients were younger than 10 years. By the time of diagnosis, 9 patients had local diseases, and the other 5 patients had metastatic diseases. All the patients' diagnoses were confirmed by pathological studies. Nine patients had Ewing's sarcoma by histology, and the other 5 patients had peripheral primitive neuroectodermal tumors (PPNET). All of the patients were treated with multidisciplinary therapy, and RS-2002 Protocol for chemotherapy was used to treat patients with rhabdomyosarcoma in our hospital. Surgery and irradiation were performed for local control. Imaging studies were used for evaluation, reevaluation and follow-up.</p><p><b>RESULTS</b>Till April 30th 2007, 13/14 patients survived. The median follow-up time was 41 months (range: 7 months-115 months). The 10-year overall survival (OS) was 88.9%+/-10.5%, and the 10-year disease-free-survival (DFS) was 72.2%+/-13.8%; 3/14 patients had disease relapse, the median time to relapse from initial diagnosis was 23 months (range: 16-30 months). One patient developed second malignancy. No therapy related death was documented.</p><p><b>CONCLUSIONS</b>Childhood Ewing's sarcoma family tumors were not very rare, and the prognosis was acceptable with optimal treatment. RS-2002 Protocol was effective and safe in treating such patients.</p>

Relationship between immunological characteristics and prognosis in children with acute myeloid leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The prognostic significance of immunophenotyping in acute myeloid leukemia (AML) has been controversial. This study investigated the relationship of immunophenotypes with French-American-British (FAB) subtypes and chromosomal abnormalities and assessed the prognostic value of immunophenotyping in children with AML.</p><p><b>METHODS</b>From January 1998 to May 2003, 75 children with newly diagnosed AML were enrolled on protocol AML-XH-99. Immunophenotypes were measured with the flow cytometry. According to the McAbs used, the patients were classified into five groups: panmyeloid antigens (CD13, CD33, and MPO), myeloid-lineage associated antigens (CD14, CD15), lineage-specific antigens (CD41, GlyA), progenitor-associated antigens (CD34, HLA-DR) and lymphoid-associated antigens (CD19, CD7). The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. The distributions of EFS were compared using the log-rank test. Chi-square analysis or Fisher exact test was used to compare the differences in the distribution of biologic presenting features. A Cox proportional hazards model was used to identify independent prognostic factors.</p><p><b>RESULTS</b>At least one of panmyeloid antigens CD13, CD33 and MPO was expressed in 72 patents (97.3%). Two or more panmyeloid antigens were expressed in 45 patients (60.8%). The proportion of children with AML expressing one or more of the lymphoid-associated antigens was 24.3%. Lymphoid-associated antigen CD19 was expressed by blast cells in most of FAB M2 patients. The patients with acute promyelocytic leukemia were characterized by the absence of HLA-DR and lymphoid-associated antigens CD19 and CD7. Monovariate analysis showed immunophenotypes were not related to the complete remission rate after the first induction course and the 5-year-EFS. Multivariate analysis suggested immunophenotyping had no independent prognostic value in AML.</p><p><b>CONCLUSIONS</b>Immunophenotyping can not be used independently in the evaluation of risk classification in children with AML. However, it is useful in the reorganization of special types of AML.</p>

Tandem application of flow cytometry and polymerase chain reaction for choice targets of minimal residual disease in childhood acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Minimal residual disease (MRD) is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). Flow cytometry and PCR are two common techniques for examining MRD in ALL. This study aimed to identify MRD targets by tandem application of both techniques in children with ALL.</p><p><b>METHODS</b>From September 2001 to October 2003, 126 children with newly diagnosed ALL were enrolled on the treatment protocol ALL-XH-99. Tandem application of flow cytometry and PCR was performed to identify MRD targets in these patients.</p><p><b>RESULTS</b>1. Using sets of combined antibodies, immunophenotypic expression of leukemia cells was observed in 95 of 106 B-lineage ALL cases (89.6%). Only one aberrant immunophenotype was observed in 11 cases (11.6%) and most patients with B-lineage ALL (88.4%) expressed at least two suitable targets. 2. Using PCR technique, T-cell receptor (TCR) or immunoglobulin gene rearrangements were identified in 26 of 27 patients (96.3%). Two or more monoclonal/ bi-allelic gene rearrangements were identified in 17 cases (65.4%). The majority (70%) of T-lineage ALL cases contained TCRVgammaI-Jgamma1.3/2.3. Cross-lineage TCR rearrangements were found in 57.1% of cases with B-lineage ALL. 3. Suitable MRD targets of immunophenotypic abnormalities or antigen receptor gene rearrangements were detected in 121 patients (96.0%).</p><p><b>CONCLUSIONS</b>MRD targets were identified using tandem application of flow cytometry and PCR in almost of children with ALL. Cross-lineage TCR rearrangements and bi-allelic gene rearrangements were observed in many patients.</p>

Clinical characteristics and treatment outcome of 36 cases with non-Hodgkin's lymphoma arising from mediastinum in children / 中华儿科杂志

<p><b>OBJECTIVE</b>Non-Hodgkin's lymphoma (NHL) presenting as mediastinal mass is usually progressive and may cause severe respiratory distress and death. This study aimed to summarize the clinical features and prognosis of NHL arising from mediastinum.</p><p><b>METHODS</b>Totally 36 patients with NHL arising from mediastinum reported herein were diagnosed between 1999 and 2007. Their clinical characteristics, pathologic classification, diagnosis, outcome of different treatment protocol were retrospectively analyzed. Of these 36 patients, 25 were male, 11 were female (2.2:1). The mean age was 7.9 (range 1 - 12) years. Diagnosis was established on pathology that was achieved by mediastinal mass or peripheral lymph nodes biopsy, while some were diagnosed based on bone marrow or pleural effusion cytology study and immunophenotyping. For staging, the St. Jude system was applied. Patients received T-NHL-CCCG97, T-NHL-2002 or B-NHL-2001 protocol according to morphology and immunophenotyping. Patients who experienced superior vena cava syndrome (SVCS) and/or superior mediastinum syndrome (SMS) received induction chemotherapy with cyclophosphamide (C), vincristine (O) and prednisone (P) for one week.</p><p><b>RESULTS</b>Twenty-seven cases experienced mediastinal mass or peripheral lympho nodes biopsy and were diagnosed by histopathology and immunohistochemistry. Of them, 24 were lymphoblastic lymphoma and 3 were anaplastic large cell lymphoma. Nine patients were diagnosed by cytological study of bone marrow aspiration or pleural fluid. All the 36 cases were T-cell type. Twenty-four cases were in stage III, 12 in stage IV. Twenty-four patients had urgent situation of SVCS and airway obstruction, 22 patients reached good response after emergency management including COP induction chemotherapy and pleural effusion suction. Twenty-nine cases achieved complete remission (CR) while in 6 patients the disease relapsed. Thirteen patients died from disease progression, relapse or severe infection during chemotherapy. The Kaplan-Meier estimate of 5-year progression-free survival (PFS) was 61% +/- 8% (median follow up 35 months) for these 36 patients.</p><p><b>CONCLUSION</b>Establishment of a diagnosis as soon as possible was important to reduce the mortality and improve long term survival of patients. Induction chemotherapy for emergency situation was efficacious. The regimen of T-NHL-CCCG97, T-NHL-2002, and B-NHL-2001 for NHL arising from mediastinum based on pathological classification is feasible.</p>

Effectiveness of the AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia (APL) in children.</p><p><b>METHODS</b>Thirty-three children with APL received AML-XH-99-M3 protocol treatment. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were evaluated by the Kaplan-Meier medthod with SPSS13.0 software.</p><p><b>RESULTS</b>Thirty patients (90.9%) achieved a complete remission (CR) after one course of treatment. The total CR rate was 100%. Six patients (18.2%) relapsed in an average of 29.17 months (16-38 months). Two patients (6.1%) died. The 7-year EFS and DFS in the 30 patients were 73.4+/-9.4%. The overall survival rate was 91.2+/-6.0%. The difference of EFS was observed in patients receiving intermittent all-trans-retinoic acid (ATRA) administration or not in the maintenance therapy (88.9+/-10.5% vs 62.5+/-13.6%) (P<0.05).</p><p><b>CONCLUSIONS</b>The AML-XH-99-M3 protocol for the treatment of APL produced a higher CR rate and higher EFS, DFS and OS rates in children. Intermittent administration of ATRA in the maintenance therapy can improve EFS rate.</p>

Evaluation of a modified induction chemotherapy in children with acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the treatment outcome of children with acute lymphoblastic leukemia (ALL), and to evaluate the efficacy and safety of a modified induction chemotherapy between the two protocols used to treat children with ALL in Shanghai Children's Medical Center.</p><p><b>METHODS</b>From Jan. 1st, 1999 to Mar. 1st, 2006, 311 patients with newly diagnosed childhood ALL, who underwent induction chemotherapy for over 10 days, were eligible for analysis. Group 99 (n = 243) patients who were admitted before May 1st, 2005, were treated with ALL-XH-99 Protocol, whereas 68 patients admitted afterwards, defined as Group 05, were treated with ALL Protocol 2005 which was based on ALL-XH-99 Protocol but the treatment intensity was reduced to decrease treatment associated mortality. Clinically, the distributions of the initial data from the patients, treatment responses, complete remission rates after therapy, and treatment-associated infections in the two groups were evaluated.</p><p><b>RESULTS</b>Patients from the two groups obtained similar complete remission rate (91.8% vs. 95.6%, P = 0.29), while patients from Group 05 were benefited more from their therapy. They had lower therapy associated infection rate (23.5% vs. 54.7% in Group 99, P < 0.01), and no severe infection (0 vs. 9.1% in Group 99) and no infection related death occurred (0 vs. 3.7% in Group 99). Patients in the Group 05 also had shortened period from the beginning day of the initial therapy to complete remission (32.34 +/- 3.36 days vs. 34.18 +/- 4.96 days, P < 0.01).</p><p><b>CONCLUSIONS</b>ALL Protocol 2005 had the same efficacy as ALL-XH-99 Protocol had in the induction therapy in treating children with ALL, but it was safer than ALL-XH-99.</p>

Comprehensive protocol for diagnosis and treatment of childhood neuroblastoma--results of 45 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>The aim of the paper was to improve the prognosis of neuroblastoma (NB) stage III and IV in children through the comprehensive therapy including chemotherapy, delayed tumor resection, autologous stem cell transplantation (ASCT) and inducing differentiation and to analyze the factors affecting the prognosis.</p><p><b>METHODS</b>Newly diagnosed neuroblastoma patients seen from Oct.1998 to Dec.2003 were divided into high, medium and low risk groups depending on clinical stage and age. Comprehensive protocol included accurate staging, delayed and/or second tumor resection for stage III and IV patients, chemotherapy of different intensity mainly composed of cell cycle nonspecific drugs and 13-cis-retinoid for inducing cell differentiation. ASCT was given at the end of therapy for high risk group.</p><p><b>RESULT</b>Forty-five patients, 6 months to 11 years of age, 32 males and 13 females, were analyzed. Of them, 15 were found to have the tumor in adrenal gland, 12 had the tumor extended to the retro-peritoneal space, while in 15 cases the tumor was beside the spinal column in chest and in 3 the tumor was located in other places. Nine cases had stage I, 1 case had stage II, 8 cases had III, 26 cases had stage IV and 1 case had stage IVs of the tumor. Depending on the age and stage of the tumor, 26 cases were aligned into high risk protocol, 10 into medium risk and 9 into low risk groups. Thirty nine cases were treated as planned. Eleven of them received ASCT including 2 cases who received second ASCT. Of the thirty-nine patients, 31 achieved complete remission (CR) and 8 partial remission (PR) after surgery and/or chemotherapy. During up to 21 months median following up period (range 14 to 64 months), 24 cases (62%) kept CR (median 22 months) and 4 survived with stable disease. The survival rate (SR) was 72%. Eleven cases died of relapse and disease progression. No death occurred from treatment complication. Statistical analysis showed that the age older than 18 months, and stage III and IV of the tumor were the factors predicting poor prognosis (P = 0.04 and 0.003, respectively). Patients who had the tumor originated from the retroperitoneal space, who had incomplete tumor resection, and those who did not receive ASCT had poorer prognosis, but the differences were not significant (P = 0.092, 0.55 and 0.60, respectively).</p><p><b>CONCLUSION</b>The comprehensive protocol seemed to be reasonable. Age older than 18 months, and stage III and IV were the factors suggesting poor prognosis. The origin of the tumor, completeness of tumor resection, and use of ASCT had no significant impact on the prognosis.</p>

Analysis of prognostic variables in childhood acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prognostic value of the biological features and therapy-related factors in childhood acute myeloid leukemia (AML).</p><p><b>METHODS</b>From January 1998 to May 2003, 75 patients with newly diagnosed AML were enrolled on the protocol AML-XH-99. Biological features at presentation [gender, age, white blood cells, platelet count, French-American-British (FAB) subtypes, cytogenetic abnormalities] and therapy-related factors [bone marrow (BM) blast cell counts at 48 h after the first induction course, complete remission (CR) rate after the first course of induction therapy] were analyzed. The probability of event-free survival (pEFS) was estimated by Kaplan-Meier analysis and the distributions of pEFS were compared using log-rank test. Chi-square analysis or Fisher exact test was used to compare differences in the distribution of presenting biological features. A Cox proportional hazards model was used to identify independent prognostic factors.</p><p><b>RESULTS</b>(1) Univariate analysis of the proportion of patients attaining CR after induction indicate that FAB M(5), BM blasts >or= 0.150 at 48 h after the first induction course and no response to the first induction course were associated with lower CR rates (P = 0.001, 0.011, 0.000 respectively). Univariate analysis also demonstrated that the 5-year pEFS for patients with age < 1 year or > 10 years, platelet count < 20 x 10(9)/L, FAB M(5), hepatomegaly, BM blasts >or= 0.150 at 48 h after the first induction course and no response to the first induction course, central nervous system (CNS) leukemia was unfavorable, while the outcome of patients with cytogenetic abnormalities of t (8; 21) or t (15; 17) were better. (2) Multivariate analysis suggested that cytogenetic abnormality of t (15; 17), achieved CR after the first induction course and no CNS leukemia were independent favorable prognostic factors.</p><p><b>CONCLUSIONS</b>Combined analysis of cytogenetic abnormalities with early treatment response has an important prognostic significance, and can predict outcomes.</p>

Prognostic value of minimal residual disease in childhood B-cell acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prognostic value of minimal residual disease (MRD) in childhood B-cell acute lymphoblastic leukemia (ALL) after induction chemotherapy.</p><p><b>METHODS</b>From September 2001 to October 2004, 102 patients with newly diagnosed B-ALL were enrolled in protocol ALL-XH-99. MRD after induction therapy, before high-dose methotrexate and early intensification as well as at 1 year and 2 year maintenance therapy was detected by multiparameter-flow-cytometry (MP-FCM).</p><p><b>RESULTS</b>(1) The probability of 39-month event-free survival (EFS) for patients with a level of MRD < 10(-4), was significantly higher than for those with a higher MRD [(83.00 +/- 9.90)% vs 0.00%, P < 0.01]. (2) Univariate analysis indicated that the MRD level at achieving complete remission (CR) had no relationship with the biologic features at presentation (gender, age, white blood cells and cytogenetic abnormalities), but did with Philadelphia chromosome, the time reaching CR, ALL-XH-99 risk group and lymphoblasts in bone marrow on day 19 after induction therapy (P < 0.05). (3) Multivariate analysis suggested that MRD level after the first induction course was an independent prognostic factor (hazard ratio, 5.381; 95% CI 0.004 to 0.624; P < 0.05).</p><p><b>CONCLUSION</b>The MRD level at achieving CR is one of important prognostic factor in the treatment of childhood B-cell ALL, and might be used to assess the early treatment response.</p>

Correlation between karyotypic characteristics and treatment outcome in childhood acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the relationship between karyotypic characteristics and treatment outcome of childhood acute lymphoblastic leukemia (ALL) and compare the difference in karyotypic aberration between ALL patients in China and in western countries.</p><p><b>METHODS</b>From January 1998 to May 2003, 193 patients with newly diagnosed ALL were enrolled on protocol ALL-XH-99. The patients were classified into 4 groups according to the karyotype of the leukemia cells: normal karyotype, hypodiploid, hyperdiploid and pseudodiploid. Event-free survival (EFS) was estimated by Kaplan-Meier analysis and the distributions of EFS were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.</p><p><b>RESULTS</b>(1) Of 193 ALL patients, 115 had cytogenetic data. There were 53 (46.09%) with normal karyotype, 29 (25.22%) hyperdiploid, 9 (7.83%) hypodiploid, 4 coexpression of hypodiploid/hyperdiploid and 20 (17.39%) pseudodiploid. The probability of 5-year EFS for the four subgroups were (78.28 +/- 6.34)%, (86.07 +/- 6.47)%, (53.85 +/- 13.83)% and (40.10 +/- 12.17)%, respectively (P = 0.0041). (2) The clinical presentation and early response to treatment had no difference among the four groups, but the events are significantly different. (3) The probability of 5-year EFS for the combined hypodiploid group and the non-hypodiploid group was (53.85 +/- 13.83)% and (69.98 +/- 5.94)%, respectively (P = 0.1281). (4) The probability of 4-year EFS was significantly worse for patients with Philadelphia chromosome than for no Philadelphia chromosome patients [(28.57 +/- 17.07)% vs (70.85 +/- 5.60)%, P = 0.0009]. (5) Multivariate analysis suggested that the karyotypic characteristics, Philadelphia chromosome, age < 1-year or > 12-year, and white blood cell counts were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The cytogenetic pattern of Chinese childhood ALL patients was similar to that of western countries. Cytogenetic findings especially Philadelphia chromosome had important prognostic significance.</p>

Failure of treatment and protocol compliance in patients with acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the main reason of failure in treatment and compliance to protocol in children with acute lymphoblastic leukemia (ALL) at a single institute which is located at the most developed city of China.</p><p><b>METHODS</b>All the ALL patients who were diagnosed at the hospital from October 1998 to June 2003 were analyzed. The data were extracted from the department's tumor registry database. Failure in protocol compliance and treatment was analyzed within different risk groups, patients' resident area, and time period. The patients who had not received any therapy after ALL diagnosis were accounted as early protocol compliance failure, those who received therapy for less than 15 days were regarded as interim failure in protocol compliance, and those who gave up therapy or were lost in follow-up after 15 days with stable disease or complete remission (CR) were accounted as late compliance failure.</p><p><b>RESULTS</b>Totally 224 patients were diagnosed to have ALL, of them 38 patients went home without receiving any therapy, i.e., the rate of early protocol compliance failure was 17.1%. Of the remaining 186 patients, 22 (10.5%) belonged to interim protocol compliance failure, and 6 cases discontinued the therapy after 15 days treatment, who were classified into late compliance failure. Six cases (10.5%) were regarded as protocol compliance failure among 57 Shanghainese, and so were 22 cases (17.1%) out of 129 non-Shanghainese. There was no significant difference between the two groups (chi(2) = 1.332, P > 0.05). Up to a median 40 months follow-up showed that in 52 patients (31.7%) the treatment failed, of which 37 cases (22.6%) died of incomplete response and relapse, and 15 cases (9.5%) died of therapy complication. Among different risk groups, 24 cases (47.1%) came from high risk group, 18 (34.0%) from medium risk group, and 5 (9.4%) from low risk group. Very significant difference was found among the different risk group (chi(2) = 21.463, P < 0.01). Treatment failure was 28.6% (32/112) in non-Shanghainese and 38.5% (20/52) in Shanghainese. Total failure in protocol compliance and treatment was 42.9% (32 + 22/129) in non-Shanghainese and 45.6% (20 + 6/57) in Shanghainese. The difference of treatment failure was not significant different between the two groups (chi(2) = 1.354, P > 0.05).</p><p><b>CONCLUSION</b>Protocol compliance failure is the reason as important as the treatment failure for childhood ALL management failure. Either failure should not be neglected. Death from complications was relatively high which needs more attention, especially during induction period. Unusually high death rate occurred in high and medium risk group patients. The grouping criteria may need modification.</p>

Prognostic value of both detection of lymphoblasts in the period of early treatment and minimal residual disease in childhood acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prognostic value of both morphological persistent disease on day 19, on complete remission (CR) and minimal residual disease (MRD) in the bone marrow (BM) after multiagent remission induction therapy.</p><p><b>METHODS</b>From January 1998 to May 2003, 193 patients with newly diagnosed ALL were enrolled on protocol of ALL-XH-99. BM blast counts on day 19 and on CR after induction therapy were examined. BM MRD at the end of induction therapy was detected by MP-FCM.</p><p><b>RESULTS</b>(1) The probability of 5-year event-free survival (pEFS) was significantly worse for patients with > or = 0.050 BM lymphoblasts on day 19 than that with < 0.050 BM lymphoblasts [(42.59 +/- 14.28)% vs (74.24 +/- 6.67)%, P < 0.001]. (2) The 5-year pEFS was significantly worse for patients with a low percentage of lymphoblasts (< 0.050) in BM on CR as compared to those with no morphological persistent lymphoblasts [(63.47 +/- 9.23)% vs (76.41 +/- 6.09)%, P < 0.05]. (3) No significant difference was found in BM lymphoblasts between patients with MRD (> or = 10(-4) of nucleated bone marrow cells) and those without MRD (< 10(-4)) at the end of induction therapy (P > 0.05). The 22-month pEFS was significantly worse for patients with MRD as compared with those without MRD on CR [(23.81 +/- 20.26)% vs (94.44 +/- 5.40)%, P = 0.001].</p><p><b>CONCLUSIONS</b>BM lymphoblast > or = 0.050 on day 19 after induction therapy is an independent prognostic factor for childhood ALL; low percentage of lymphoblasts and minimal residual disease in BM on remission also do it. Patients with > or = 0.050 lymphoblast in BM on day 19 or with MRD > or = 10(-4) at the end of induction therapy should receive altered and more intensive chemotherapy.</p>

Treatment of advanced malignant solid tumors in children with autologous hematopoietic stem cell transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of autologous hematopoietic stem cell transplantatation in children with advanced solid tumors.</p><p><b>METHODS</b>Bone marrow was collected from the anterior crista of iliac in both sides in 13 cases while peripheral mononuclear cell was harvested with CS-3000 cell separator in other 15 patients after G-CSF mobilization. Since one of them was suspected to have bone marrow involvement of the neuroblastoma cells, the autograft was purged with CliniMACS based on the CD34 positive selection. Conditioning regimen was CBV protocol (cyclophosphamide + bischloro-nitrosourea, i.e., BCNU + etopside) in two children with Hodgkin's disease and etopside plus carboplatin plus melphalan in others.</p><p><b>RESULTS</b>The number of mononuclear cells collected from bone marrow or peripheral blood was equal to (5.4 +/- 2.1) x 10(8)/kg and (4.1 +/- 1.9) x 10(8)/kg, respectively. Hematopoietic reconstitution was achieved in all patients. Mean time of the neutrophil count recovery to 0.5 x 10(9)/L and mean time of platelet recovery over 2.0 x 10(9)/L were 11.8 +/- 5.7 and 21.0 +/- 9.3 days, respectively. Three units of packed red blood cells and three units of platelet products were transfused in the course of transplantation on average. A total of 12 children developed neutropenic fever and 3 of them had positive blood culture, including staphylococcus epidermal, staphylococcus saprophyte and bacillus subtilis. None of the children died of transplantation-associated complication. One child developed acute renal failure, pulmonary edema and pericardial effusion followed by respiratory distress syndrome. Mechanical ventilation and pulmonary surfactant were used and the patient recovered at last. Another patient developed BCNU associated pulmonary injury, severe pulmonary hypertension and eosinophilosis and recovered after treatment. The mean follow up time was 13 months. Among the 27 children, five died of relapse 5 months after transplantation, and one case of NHL had CNS involvement 3 months after transplantation but has got 17 months of survival till now. The remaining twenty one children were in status of disease-free survival.</p><p><b>CONCLUSION</b>Autologous stem cell transplantation might be effective in the treatment advanced solid tumors in children.</p>

Analysis of therapeutic effectiveness in 158 childhood acute lymphoblastic leukemia patients treated with ALL-XH-99 protocol / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the treatment outcome of 158 childhood acute lymphoblastic leukemia (ALL) patients, and explore how to improve the event-free survival (EFS) rate in ALL.</p><p><b>METHOD</b>All of the patients entered the ALL-XH-99 clinical trial. Kaplan-Meier method was used to estimate survival rates and differences were compared with the 2-sided log-rank test, statistics was done by SPSS.</p><p><b>RESULTS</b>Out of the 158 patients, 153 (96.8%) attained complete remission (CR) in a median time of 33 days. The overall EFS rate at 5 years was (72.4 +/- 7.8)% with a median observation duration of 26 months. The EFS rates at 5 years in low-risk (LR), median-risk (MR) and high-risk (HR) groups were (88.9 +/- 5.5)%, (78.5 +/- 8.0)% and (53.4 +/- 10.9)%, respectively (P < 0.05). Relapse occurred in 15 patients (10.0%) in a median time of 12 months, including 13 isolated hematologic relapses, 2 isolated central nervous system (CNS) relapses. Seven patients died of complications, and 13 died of leukemia relapse.</p><p><b>CONCLUSION</b>The early response to therapy was an important independent prognostic factor, high-dose methotrexate (HD-MTX) was effective for preventing haematological and testicular relapse. The ALL-XH-99 protocol decreased the rate of therapy-related death and improved the long-term event-free survival rate.</p>

Response rate of AML-XH-99 protocol in the treatment of 82 childhood acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the outcomes of childhood acute myeloid leukemia (AML) treated with AML-XH-99 protocol and explore how to improve the event-free survival (EFS) rate.</p><p><b>METHODS</b>Eighty-two patients entered AML-XH-99 clinical trial. Survival rates were evaluated by Kaplan-Meier method with SPSS.</p><p><b>RESULTS</b>Among the 82 patients, 58 (70.7%) achieved complete remission (CR) after one course treatment, and the total CR rate was 84.1%. The overall 5 year EFS rate was (46.1 +/- 9.1)% and disease-free survival (DFS) rate was (54.3 +/- 10.3)% over a median observation period of 23 months. The 5 year EFS rate of 56 patients received high-dose cytarabine(HD-Ara-C) as intensification therapy was (47.2 +/- 12.9)%. Relapse occurred in 19 patients (26.0%) with a median time of 10 months (ranges 2 approximately 53 months), 28 patients died.</p><p><b>CONCLUSION</b>AML-XH-99 protocol resulted in a higher CR rate, especially one course CR rate, which was one of the key factors for long-term EFS and HD-Ara-C intensification therapy was effective in the treatment of childhood AML.</p>

Results of Wilms' tumor trial (WT-99) in Shanghai children's medical center / 中华儿科杂志

<p><b>OBJECTIVE</b>Wilms' Tumor Trial (WT-99) of Shanghai Children's Medical Center was designed and conducted by applying therapeutic regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria of U.S.A. The main aim of WT-99 was to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable-histology (UFH) tremors with more intensive chemotherapy.</p><p><b>METHODS</b>Diagnosis and treatment was decided by the multi-disciplinary team including oncologists, surgeons, pathologists, radiologists and diagnostic radiologists. Twenty consecutively diagnosed patients were recruited between October 1998 and October 2002. The regimen for patients at favorable-histology (FH) stage I and II and anaplastic stage I was vincristine (Vcr) and dactinomycin (Act-D) only, while for those at focal anaplastic stage II to IV and FH stage III and IV the regimen was Vcr, Act-D and adriamycin (Adr). Patients at diffuse anaplastic stage II to IV and clear cell stage I to IV received four-drug regimen including Vcr, etoposide (VP16), Adr and cytoxan (CTX). For those at rhabdoid stage I to IV the regimen was carboplatin, VP-16 and CTX. Un-resectable patients received 2 courses of Ifosfamide, Vcr and VP-16 as pre-surgery therapy. No radiation therapy was used for patients at stage I and FH stage II.</p><p><b>RESULTS</b>Twenty patients, from 7 months to 12 years old, were enrolled. Pathologic analysis showed fourteen cases were at their FH, three at unfavorable-histology (UFH), two at clear cell and one at rhabdoid stage. Five patients were at stage I, five at stage II, six at stage III, three at stage IV and one at stage V. Eighteen reached complete response (90%), and two failed. One relapsed after 24 months of CCR and reached the second CR after intensive chemotherapy. No therapy-related death happened. Survival rate (SR) was 90% (18/20) and event-free survival (EFS) was 85% (17/20) at 11-45 months, average 27 months.</p><p><b>CONCLUSION</b>Multi-disciplinary team work model and protocol WT-99 are safe and effective for Wilms' tumor.</p>

Application of CD34+ autologous peripheral progenitor cell transplant in the treatment of children with refractory SLE / 中华儿科杂志

<p><b>OBJECTIVE</b>Systematic lupus erythematosis (SLE) is a severe disease which affects the patient for many years and there is no radical cure for the disease. To explore a possible way to treat children with refractory SLE, the authors treated 2 children with grade III and IV lupus nephropathy for 5 years and 7 years respectively, mainly presented with persistent thrombocytopenia, proteinuria, pleural effusion with CD34(+) autologous peripheral progenitor cells transplantation.</p><p><b>METHODS</b>Mobilized with G-CSF and collected with CS-3000 Cell Separator, passed through the CliniMacs CD34(+) cell selection device, the count of CD34(+) cells obtained reached 1.0 x 10(6)/kg and 1.7 x 10(6)/kg, respectively with the remaining of 2.0 x 10(5)/kg and 1.0 x 10(4)/kg of CD3(+) cells individually. The selected CD34(+) cells were frozen at -80 degrees C. The conditioning regimen consisted of cyclophosphamide [50 mg/(kg x day) for 4 days] plus ATG [Fresennius S 5 mg/(kg x day) for 3 days]. After 48 h treatment with cyclophosphamide, the frozen stem cells were infused back to the patients.</p><p><b>RESULTS</b>Neutrophils recovered on 9 and 7 days after transplantation respectively in these 2 cases. Beginning from 15 days, the platelet count recovered and remained at over 100 x 10(9)/L. The sign of Cushing's syndrome disappeared completely 3 months after transplantation because discontinuing the steroid. One child's height had a 5 cm increase within 6 months after stopping steroid and this was the first height gain during the 7 years since she had had the disease. Till this paper was written, these 2 children were followed up for 13 months and 6 months, respectively, all the original symptoms and autoantibodies related to autoimmune disorders disappeared. But the cell-mediated immunity did not recover yet with the CD4(+) cell level still remained at a lower level.</p><p><b>CONCLUSION</b>The effect of CD34(+) autologous peripheral progenitor cell transplantation on the children with refractory SLE was satisfactory so far, but the long-term effect remains to be confirmed by further studies on more cases.</p>

Relationship between Expression Level of Glucocorticoid Receptor and Treatment Outcome in Children with Acute Lymphoblastic Leukemia / 实用儿科临床杂志

Objective To study the relationship between the initial expression level of glucocorticoid receptor (GR) and the treatment outcome in children with acute lymphoblastic leukemia (ALL). And to evaluate if the initial expression level of GR could be the prognostic factor for children with ALL.Methods Anti-GR-antibody was used to measure the GR expression level in the bone marrow samples from 48 newly diagnosed children with ALL with flow cytometry. Also the GR expression levels in the patients at complete remission were mea-sured. Fifteen randonmized samples from ALL patients in continuous complete remission (CCR) were measured in this study. The GR expre-ssion levels of 30 blood samples from children in control group were monitored. Results The initial GR expression level had no association with the results after therapy. The GR expression level in CR and CCR had no statistic difference compared with that in control group.Conclusions It is not clear yet if the initial GR expression level could be the prognostic factor in children with ALL. Monitoring dynamic changes of the GR expression level in children with ALL seems to be of no remarkable significance.