The prognosis of haploidentical hematopoietic stem cell transplantation in infants and patients under 3 years old with acute leukemia.

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients <3 years of age remains controversial. Data on haploidentical donor (HID) transplants in this age group is limited. PATIENTS AND METHODS: We retrospectively analyzed the prognosis of 97 patients with acute leukemia aged <3 years who underwent HID transplantation at our institute. RESULTS: With a median follow-up of 45 months, the 3-year disease-free survival (DFS), overall survival (OS), and 3-year cumulative incidence rate of treatment-related mortality were 69.3% (95% confidence interval (CI): 59.9%-78.7%), 74.2% (95% CI: 65.2%-83.2%), and 3.6% (95% CI: 0.9%-9.7%) in all 97 patients, respectively. The 3-year DFS and OS rate in patients diagnosed <1 year and patients diagnosed ≥1 year were comparable: 77.8% (95% CI: 62.2%-93.4%) versus 66.3% (95% CI: 55.0%-77.6%, p = .253) and 82.5% (95% CI: 66.3-98.7%) versus 72.8% (95% CI: 61.9%-83.7%, p = .153), respectively. At the last follow-up, 23 patients had died, and 20 had died of relapse. Multivariate analysis revealed that positive pre-HSCT flow cytometric minimal residual disease (hazard ratio 5.605, p = .000) and AML-M7 expression (hazard ratio 2.906, p = .014) were independent adverse prognostic variables for relapse. CONCLUSIONS: HID transplantation is potent and safe for infants and young patients with acute leukemia. Relapse is the primary cause of treatment failure.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

What happens to children with acute lymphoblastic leukemia in low- and middle-income countries after relapse? A single-center experience from India.

Managing a child with acute lymphoblastic leukemia (ALL) after relapse is arduous in low- and middle-income countries. A file review of children aged ≤15 years diagnosed with relapsed ALL from 2010 to 2019 was performed. Classification of relapse followed the Berlin-Frankfurt-Münster (BFM) scheme. The majority of patients were treated with a modified ALL-REZ-BFM protocol. Of 764 children treated for ALL in the study period, 163 (21.3%) relapsed. The median age at relapse was 101 months (range: 8-297). The immunophenotype was B-ALL and T-ALL in 140 (86%) and 23 (14%) patients. The site of relapse was extramedullary, combined, and medullary in 46 (28%), 45 (28%), and 72 (44%) patients. Very early, early, and late relapses were observed in 57 (35%), 66 (40%), and 40 (25%) patients. The proportions of extramedullary and medullary sites were greater among patients with early and late relapses, respectively (p = 0.039). Eighty-four (52%) patients were treated with palliative intent. The 2-year event-free survival (EFS) of patients treated with curative intent was 36.3 ± 6.3%. The 2-year EFS for very early/early and late relapses were 18.2 ± 6.2% and 67.6 ± 10.4% (p < 0.001). The 2-year EFS did not differ between extramedullary, combined, and medullary relapses. Treatment-related mortality occurred in 14 (20%) patients. More than 50% of the patients with relapse were treated with the intent of palliation. Extramedullary relapses were more likely to be early and did not have a better outcome than medullary relapses. Children with late relapse had a fair chance of survival with chemotherapy.

Development and validation of a mortality predicting scoring system for severe aplastic anaemia patients receiving haploidentical allogeneic transplantation.

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

Childhood aggressive B-cell non-Hodgkin lymphoma in low-middle-income countries.

In high-income countries (HICs) paediatric aggressive B-cell lymphomas are curable in about 90% of cases. Much worse results, with cure rates ranging from less than 30% to about 70%, are achieved in low- and middle-income countries (LMICs), where 90% of paediatric non-Hodgkin lymphomas occur. Low socio-economic and cultural conditions, the lack of optimal diagnostic procedures, laboratory facilities and adequate supportive care exert a strong negative impact on compliance, treatment delivery, toxicity and, consequently, on the clinical outcome. Published data are scarce, generally originating from single institutions, and are difficult to compare. National and international cooperation projects have been undertaken to reduce the unacceptable gap between HICs and LMICs in the management of children with cancer, by promoting the sharing of knowledge and by implementing adequate local healthcare facilities, with initial promising results. In the present review, we will summarize the results so far obtained in the management of paediatric aggressive B-cell NHL in LMICs.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting.

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Outcome and prognostic factors in childhood B non-Hodgkin lymphoma from India: Report by the Indian Pediatric Oncology Group (InPOG-NHL-16-01 study).

The literature on B-non-Hodgkin lymphoma (NHL) in India is restricted to individual hospital data. The study aimed to evaluate the epidemiology and outcome of B-NHL in our country. One hundred and ninety-one patients of B-NHL from 10 centers diagnosed between 2013 and 2016 were analyzed retrospectively. B/T lymphoblastic lymphoma and patients with inadequate data were excluded. The median age was 88 months (IQR: 56, 144) with an M:F ratio of 5.6:1. Undernourishment and stunting were seen in 36.5% and 22%. Primary site was abdomen in 66.5%. Hypoalbuminemia was noted in 82/170 (48.2%). Histological subtypes: Burkitt lymphoma (BL): 69.6%, Burkitt-like: 10.4%, and diffuse large B cell lymphoma (DLBCL): 13.6%, unclassified and others (6.4%). Stage distribution: I/II, 33 (17.3%), III, 114 (59.7%), and IV, 44 (23%). One-eighty-six patients took treatment. Protocols used were LMB and BFM in 160/186 (86%). At a median follow-up of 21.34 (IQR: 4.34, 36.57) months, the disease-free-survival (DFS) was 74.4% and event-free-survival (EFS) was 60.7%. Treatment-related mortality (TRM), relapse/progression and abandonment were 14.3%, 14.5%, and 8.4%, respectively. Bone marrow positivity, stage IV disease, and lactate dehydrogenase (LDH) > 2,000 U/l predicted inferior EFS. Stage IV disease, LDH > 2,000 U/l, bone marrow positivity, tumor lysis syndrome and low albumin predicted TRM; LDH retained significance on multivariate analysis for EFS and TRM [OR: 4.54, 95% CI: 1.14-20, p 0.03; OR 20, 95%CI: 1.69-250, p 0.017]. BL was the main histological subtype. High TRM and relapse/progression are hampering survival. An LDH > 2,000 U/l was adversely prognostic. These data demonstrate a need to develop a national protocol that balances toxicity and potential for cure.

Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma-data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin's Lymphoma Study Group).

In elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61-65 years, 66-70 years, 71-75 years, and 76-80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76-80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

Early death and treatment-related mortality: A report from SUCCOUR - Supportive Care for Children with Cancer in Africa.

BACKGROUND: Deaths during paediatric cancer treatment are common in Africa. It is often difficult to distinguish between treatment-related and disease-related causes. To prevent these deaths, it is important to study them and identify the cause. The Supportive Care for Children with Cancer in Africa (SUCCOUR) programme enabled a study with the objective to identify the reasons for early death during treatment. METHODS: We conducted a multicentre prospective, observational cohort study in sub-Saharan Africa. Children younger than 16 years with newly diagnosed cancer treated with curative intent were included from 1 September 2019 until 30 March 2020. Data were abstracted in real time by trained personnel using standardised case report forms. The treating clinician's assessment of the cause of death and signs, symptoms and laboratory values of patients who died during the first 3 months of treatment (early death) were documented. RESULTS: We included 252 patients (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Fifteen percent of patients (37/252) died during the first 3 months of treatment. Of these 37 patients, 33 (89%) died of a treatment-related cause. Treatment-related mortality of all patients in the first 3 months of treatment was 13% (33/252). CONCLUSION: Fifteen percent of patients had an early death during treatment and 13% had a treatment-related death. This suggests the need to improve supportive care. Implementation of supportive care pathways adapted to local circumstances may be helpful.

Adolescents and young adult acute myeloid leukemia outcomes at pediatric versus adult centers: A population-based study.

BACKGROUND: Adolescents and young adult (AYA) acute myeloid leukemia (AML) outcomes remain poor. The impact of locus of care (LOC; adult vs pediatric) in this population is unknown. PROCEDURE: The IMPACT cohort comprises detailed data for all Ontario, Canada, AYA aged 15-21 years diagnosed with AML between 1992 and 2012, linked to population-based health administrative data. We determined the impact of LOC on event-free survival (EFS) and overall survival (OS), treatment-related mortality (TRM), and relapse/progression. RESULTS: Among 140 AYA, 51 (36.4%) received therapy at pediatric centers. The five-year EFS and OS for the whole cohort were 35.0% ± 4.0% and 53.6% ± 4.2%. Cumulative doses of anthracycline were higher among pediatric center AYA [median 355 mg/m2 , interquartile range (IQR) 135-492 vs 202 mg/m2 , IQR 140-364; P = 0.003]. In multivariable analyses, LOC was not predictive of either EFS [adult vs pediatric center hazard ratio (HR) 1.3, 95% confidence interval (CI) 0.8-2.2, P = 0.27] or OS (HR 1.0, CI 0.6-1.6, P = 0.97). However, patterns of treatment failure varied; higher two-year incidence of TRM in pediatric centers (23.5% ± 6.0% vs.10.1% ± 3.2%; P = 0.046) was balanced by lower five-year incidence of relapse/progression (33.3% ± 6.7% vs 56.2% ± 5.3%; P = 0.002). CONCLUSIONS: AYA AML survival outcomes did not vary between pediatric and adult settings. Causes of treatment failure were different, with higher intensity pediatric protocols associated with higher TRM but lower relapse/progression. Careful risk stratification and enhanced supportive care may be of substantial benefit to AYA with AML by allocating maximal treatment intensity to patients who most benefit while minimizing the risk of TRM.

The Impact of Antibiotic-Mediated Modification of the Intestinal Microbiome on Outcomes of Allogeneic Hematopoietic Cell Transplantation: Systematic Review and Meta-Analysis.

Accumulating evidence points toward a protective role of intestinal microbiota diversity in allogeneic hematopoietic cell transplantation (allo-HCT). The purpose of this systematic review and meta-analysis is to determine the effect of antibiotic-mediated disruption of microbiota on main allo-HCT outcomes (graft-versus-host disease [GVHD], treatment-related mortality [TRM], overall survival [OS]). Following literature search, 2 reviewers screened eligible studies and assessed risk of bias (RoB). Meta-analysis was performed using Review Manager Software. Among 443 screened references, 18 were eligible for meta-analysis. In studies with genomic markers, grade II to IV acute GVHD was significantly reduced in patients not receiving gut decontamination (GD) (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.20 to 2.04). In subgroup analysis, prophylaxis with systemic antibiotics conferred an increased risk of acute GVHD (OR, 1.65; 95% CI, 1.08 to 2.53). When we incorporated RoB, we found a positive correlation of intestinal GVHD with GD (OR, 1.77; 95% CI, 1.29 to 2.44). Patients with higher microbiota diversity presented increased OS (risk ratio [RR], 1.58; 95% CI, 1.19 to 2.09) and lower TRM (RR, 0.45; 95% CI, 0.26 to 0.76). Our findings confirm that GD and prophylaxis with systemic antibiotics increase acute and intestinal GVHD. Importantly, our meta-analysis was the first to show a significant effect of microbiota diversity on TRM and OS.

Long-term follow-up of Cladribine, high-dose Cytarabine, and Idarubicin as salvage treatment for relapsed acute myeloid leukemia and literature review.

PURPOSE: Outcome for relapsed acute myeloid leukemia (AML) is poor. Cladribine has activity in AML, and an enhancing effect on other cytostatic drugs thus may help overcome resistance. Here, we present the final analysis of our phase II trial evaluating safety and efficacy of cladribine, cytarabine, and idarubicin (CAI) in relapsed AML. METHODS: Patients with relapsed AML after at least 6 months remission received two courses of CAI. After 9 patients, prolonged neutropenia prompted protocol change (omission of idarubicin in 2nd course and dose-reduction of cytarabine). Primary endpoints were remission rate and safety. RESULTS: Twenty patients received treatment, fourteen one, and six two courses CAI/CA. After first course, complete remission (CR/CRi) was achieved in 60%. Most frequent toxicity was infection. Median OS was 8.8 months in all patients and 21.1 months in those with CR. Nine patients (48%) proceeded to allogeneic stem cell transplantation (allo-SCT), four of those are still alive and in CR, accounting for a 5-year survival rate of 55% of transplanted patients. CONCLUSION: Cladribine, cytarabine, and idarubicin in relapsed AML is feasible and induces good response rates. As expected, infections are the most important complication. However, combined with allo-SCT, long-term survival can be achieved in a substantial number of patients.

Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group.

BACKGROUND: With the current more effective treatment regimens for pediatric acute myeloid leukemia (AML), research on early death (ED), treatment-related mortality (TRM), and toxicity becomes increasingly important. The aim of this study was to give an overview of the frequency, clinical features, and risk factors associated with ED and TRM in first complete remission (CR1) during the last three consecutive treatment protocols of the Dutch Childhood Oncology Group (DCOG) between 1998 and 2014. METHODS: Incidence and risk factors associated with ED and TRM in CR1 were retrospectively studied in 245 patients treated according to the Dutch ANLL-97/AML-12 (n = 118), AML-15 (n = 60), or DB AML-01 (n = 67) protocols. RESULTS: The incidence of ED was, respectively, 5.1%, 6.7%, and 3.0% excluding deaths before treatment (P = NS), and 7.4%, 11.1%, and 4.4% including deaths before the onset of treatment. Severe underweight at initial diagnosis was significantly associated with more frequent ED. When relapse was included as a competing risk, cumulative incidence of death in CR1 were 5.9%, 5.0%, and 4.6% for ANLL97, AML15, and DB01, respectively (P = NS). The most important cause of TRM included infectious and SCT-related complications. CONCLUSION: We report relatively stable rates of ED and TRM in CR1 in the latest completed DCOG protocols for newly diagnosed AML patients. The most important causes of TRM were SCT- or infection-related, warranting further evaluation and awareness.

High-Dose Melphalan and Autologous Peripheral Blood Stem Cell Transplantation in AL Amyloidosis.

AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in myeloma. This application has evolved significantly over the past three decades. This review provides a comprehensive assessment of eligibility criteria, stem cell collection, and mobilization strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies as well as long-term outcome with respect to survival, hematologic response and relapse as well as organ responses following stem cell transplantation. Continued efforts to refine patient selection and management, and incorporate novel anti-plasma cell agents in combination or sequentially to further improve outcomes in AL amyloidosis are also discussed.

Syrian and Turkish children with cancer: a comparison on survival and associated factors.

Cure rates of childhood cancer need to be improved in low-income countries and vulnerable populations such as refugees. We aimed to compare the outcome and associated factors in Syrian refugee and Turkish children with cancer treated at our hospital.Files of patients were reviewed for age, tumor type, stage, treatment, compliance to treatment, relapse or progression status, outcomes, secondary malignancy (SM) and treatment-related mortality (TRM). Overall (OS) and event-free survival rates (EFS) were analyzed.105 refugees and 304 Turkish children were treated between January 2012 and January 2019. Median age and median follow-up time were significantly lower in the Syrian group (p=0.046, p<0.001, respectively). Metastatic or advanced-stage disease was significantly more frequent in refugees (p=0.002). Relapse or progression and poor compliance to treatment were more common in refugees (p=0.01, p<0.001, respectively). Rates of OS were 55.7% and 69.7%, EFS were 28.9% and 55.7% in Syrian and Turkish patients. OS and EFS were lower in refugees compared to Turkish patients (p=0.01, p<0.001, respectively). EFS was significantly lower in refugees with poor compliance to treatment (p<0.001). TRM was reported in 12 (8 Syrian, 4 Turkish) patients. SM was detected in 3 (2 Turkish, 1 Syrian) children.Inferior survival rates were detected in Syrian refugee children compared to Turkish children. Besides from cancer-specific factors such as stage and tumor type, a series of barriers in accessing cancer care resulting in poor compliance to treatment might have been responsible from lower survival rates in Syrian children.

Effect of socio-economic status & proximity of patient residence to hospital on survival in childhood acute lymphoblastic leukaemia.

BACKGROUND & OBJECTIVES: : Survival in paediatric acute lymphoblastic leukaemia (ALL) in lower/middle income countries continues to lag behind outcomes seen in high-income countries. Socio-economic factors and distance of their residence from the hospital may contribute to this disparity. This study was aimed at identifying the impact of these factors on outcome in childhood ALL. METHODS: : In this retrospective study, file review of children with ALL was performed. Patients were treated with the modified United Kingdom (UK) ALL-2003 protocol. Details of socio-economic/demographic factors were noted from a web-based patients' database. Modified Kuppuswamy scale was used to classify socio-economic status. RESULTS: : A total of 308 patients with a median age of five years (range: 1-13 yr) were studied. Patients belonging to upper, middle and lower SE strata numbered 85 (28%), 68 (22%) and 155 (50%). Nearly one-third of the patients were underweight. There was no treatment abandonment among children whose mothers were graduates. Neutropenic deaths during maintenance therapy were lower in mothers who had passed high school. In patients who survived induction therapy, the five year event-free survival (EFS) of upper SE stratum was significantly better 78.7±4.9 vs. 59±7.2 and 58.1±4.6 per cent in middle and lower strata (P =0.026). Five year overall survival was higher in the higher SE group; being 91.2±3.5, 78.3±5.6 and 78.8±3.9 per cent (P =0.055) in the three strata. Survival was unaffected by a distance of residence from treating centre or rural/urban residence. High-risk and undernourished children had a greater hazard of mortality [1.80 (P =0.015); 1.98 (P =0.027)]. INTERPRETATION & CONCLUSIONS: : Our findings showed that higher socio-economic status contributed to superior EFS in children with ALL who achieved remission. Undernutrition increased the risk of mortality.

Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis.

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a therapeutic modality for severe systemic sclerosis (SSc). We set out to systematically review and meta-analyze the efficacy and safety of AHSCT in SSc. Randomized controlled trials (RCTs) and retrospective studies comparing AHSCT with standard immunosuppressive therapy were included. Of 363 titles screened from multiple databases, 15 were extracted for further investigation, and 4 met inclusion criteria (3 RCTs and 1 retrospective analysis). The control arm was monthly cyclophosphamide in all the RCTs and the majority of patients in the retrospective analysis (69%). Compared with the control, AHSCT reduced all-cause mortality (risk ratio [RR], .5 [95% confidence interval, .33 to .75]) and improved skin thickness (modified Rodnan skin score mean difference [MD], 10.62 [95% CI, -14.21 to 7.03]), forced vital capacity (MD, 9.58 [95% CI, 3.89 to 15.18]), total lung capacity (MD, 6.36 [95% CI, 1.23 to 11.49]), and quality of life (physical 36-Item Short Form Health Survey [MD, 6.99 (95% CI, 2.79 to 11.18)]). Treatment-related mortality considerably varied between trials but was overall higher with AHSCT (RR, 9.00 [95% CI, 1.57 to 51.69]). The risk of bias for studies included in the analysis was low. Overall, AHSCT reduces the risk of all-cause mortality and has properties of a disease-modifying antirheumatic treatment in SSc. Further investigation is warranted for refining patient selection and timing of transplantation.

Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation.

The recovery of myeloid-derived suppressor cells (MDSCs) and its relevance in clinical acute graft-versus-host disease (GVHD) and post-hematopoietic stem cell transplantation (HSCT) infections remain to be fully characterized. We examined the expansion of circulating monocytic (M-) MDSCs and granulocytic (G-) MDSCs at the time of engraftment in 130 patients undergoing allogeneic HSCT (allo-HSCT). Compared with the G-MDSC group, the high M-MDSC group had a higher infection rate within 100 days, along with worse 1-year cumulative incidence of treatment-related mortality (TRM) and 2-year probability of event-free survival (EFS). The frequency of M-MDSCs was associated with preceding severe mucositis. Transcriptome profiling analysis of 2 isolated MDSC subtype showed significantly greater matrix metalloproteinase-9 (MMP-9) expression in M-MDSCs than in G-MDSCs. M-MDSCs produced abundantly more MMP-9. Importantly, compared with G-MDSCs, M-MDSCs isolated from patients post-HSCT had a greater capacity to suppress T cell responses, and MMP-9 blockade more forcefully inhibited their immunosuppressive effect. MMP-9 levels also were associated with the occurrence of infections and with transplantation outcomes. Based on these findings, we identify M-MDSCs as a major contributor to infections early after allo-HSCT and worse clinical outcomes via MMP-9.