X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India.

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

An International Survey of Allogeneic Hematopoietic Cell Transplantation for X-Linked Agammaglobulinemia.

PURPOSE: X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by variants in Bruton's tyrosine kinase (BTK). XLA patients require lifelong immunoglobulin replacement therapy (IgRT). Only few XLA patients are indicated for allogeneic hematopoietic cell transplantation (HCT) because of severe complications. Accordingly, the published transplantation experience in XLA is minimal. We aimed to collect clinical data of XLA patients who received HCT in an international framework and to establish appropriate transplantation criteria and methods for XLA patients. METHODS: XLA patients were recruited through a questionnaire and a literature review. The data are on patient characteristics and transplantation methods and outcomes. RESULTS: In this study, twenty-two XLA patients who underwent HCT were recruited. The indication for HCT was recurrent or life-threatening infection in sixteen patients, malignancy in three, and other factors in three. A myeloablative conditioning, reduced toxicity myeloablative conditioning (RT-MAC), and reduced intensity conditioning (RIC) were selected in four, ten, and eight patients, respectively. Engraftment was achieved in 21 patients (95%). In all patients, 2-year overall survival (OS) and event-free survival (EFS) were 86% and 77%, respectively. In patients who received RT-MAC or RIC using treosulfan, busulfan, or melphalan, 2-year OS and EFS were 82% and 71%, respectively. Finally, twenty-one patients (95%) obtained complete or stable high-level mixed chimerism (50-95%), and the 1-year discontinuation rate of IgRT was 89%. CONCLUSION: Based on the concept in which IgRT is the standard treatment for XLA, HCT may be an effective and safe alternative treatment option for XLA patients, and IgRT can be discontinued following transplantation. It is ideal to perform HCT in XLA patients for whom transplantation is indicated before they develop organ damage.

Post-transplant strategies to improve relapse-free survival in childhood leukemia: Whole blood donor lymphocyte infusions and lenalidomide for inducing graft-versus-leukemia effect.

INTRODUCTION: Post-transplant graft-versus-leukemia (GVL) effect has been shown to be an important determinant of a successful outcome following hematopoietic stem cell transplantation (HSCT) in children with acute leukemia. PATIENTS AND METHODS: We performed a retrospective analysis of the children up to 18 years of age with acute leukemia who underwent HSCT between November 2002 and November 2018. GVL induction strategies included whole blood donor lymphocyte infusions (DLI) and/or lenalidomide. RESULTS: A total of 134 children were included with engraftment in 125 children (93%). Acute graft-versus-host disease (GVHD) was documented in 85 (63%) children without any induction strategies. GVL induction strategies were employed in 19 children (14%); DLI (n = 12), Lenalidomide (n = 2), DLI + lenalidomide (n = 5). Among the 19, 12 children (63%) are alive without relapse; 6 children died of relapse (31%). Among the 6 who died of relapse despite induction strategies, 5/6 had ALL and one child had AML. GVL induction was effective in preventing relapse in 7/12 (58%) children with ALL and 5/6 (83%) children with AML. Relapse-free survival in the cohort is 73/134 (55%) with a median follow-up of 32 months. GVHD of any grade was significantly associated with a lower risk of relapse (p = .008). Median survival time was 160.3 days (range 132-187) in those with chronic GVHD versus 88.3 days (range 68-107) in those without (p value = .004). CONCLUSION: Pre-emptive whole blood DLIs in graded aliquots, and lenalidomide are important tools for post HSCT GVL induction, which significantly impacts relapse-free survival in childhood leukemia.

Management of Peripheral T-Cell Lymphoma in Children and Adolescents Including STAT 3 Mutation Hyper-IgE Syndrome: One Size Does Not Fit All.

Peripheral T-cell lymphoma (PTCL) is a rare form of lymphoma in children with limited published data on treatment and lack of a uniformly accepted treatment algorithm. We retrospectively analyzed the data in children up to 18 years of age diagnosed to have PTCL from January 2016 to June 2020. The study included six children with a median age of 10 years, the youngest being a 7-month-old girl. According to the WHO-PTCL classification, three had PTCL-not otherwise specified (NOS), 2 had hepatosplenic TCL, and 1 had subcutaneous panniculitis-like TCL. All children had presented with advanced disease, 4 in St. Jude stage IV, 2 in St. Jude stage III. Three children received CHOEP chemotherapy including cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, while 1 child received CHOP. Two children received induction as per acute lymphoblastic leukemia followed by Bendamustine. Two patients succumbed to progressive disease, the infant with PTCL-NOS and 1 child with hepatosplenic TCL. Three children were in remission (median follow up of 44 mo). One child with PTCL-NOS Stage IV had an underlying STAT3 mutated hyperimmunoglobulin E syndrome and was in remission 12 months post a matched unrelated donor hematopoietic stem cell transplantation. He had grade 4 skin graft versus host disease and required extracorporeal photopheresis and ibrutinib, to which he had responded. CHOEP chemotherapy is well-tolerated and subcutaneous panniculitis-like TCL has the best prognosis thus far.

A report of haploidentical allogeneic haematopoietic stem cell transplantation for inherited bone marrow failure in Sri Lanka.

Abstract: Bone marrow failure (BMF) in children can be idiopathic (70-80%) or inherited. Haematopoietic stem cell transplantation (HSCT) is the only cure for both causes. Allogeneic HSCT requires a suitable donor. Many children will not have a HLA matched sibling or unrelated donor. A haploidentical donor is available for all children as eaazch parent will have at minimum a 50% HLA match. This report of a 7-year old girl with BMF treated with a haplo-HSCT, the first in Sri Lanka, highlights the importance of developing a haploidentical HSCT programme as a potential cure for a disease with a dismal outcome.

A comprehensive molecular study identified 12 complementation groups with 56 novel FANC gene variants in Indian Fanconi anemia subjects.

Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.

Risk-adapted therapy for the management of cytokine release syndrome in children undergoing unmanipulated haploidentical stem cell transplantation.

BACKGROUND: We aimed to describe an algorithm for the management of cytokine release syndrome (CRS) associated with haploidentical hematopoietic stem cell transplantation (haploSCT). PATIENTS AND METHODS: We performed a prospective study where children up to 18 years of age undergoing haploSCT with post-transplant cyclophosphamide from September 2014 to March 2020 were included. Supportive care included low-dose adrenaline, high-flow nasal cannula, and N-acetylcysteine (NAC). Methylprednisolone and tocilizumab were administered in the peri-engraftment phase for grade 2 CRS or one-log increase and grade 3 CRS or a two-log increase in ferritin, respectively. RESULTS: Data were analyzed in 135/148 children as 13 children died before engraftment due to sepsis. CRS was noted in 97% transplants (grade 1-74.1%, grade 2-15.6%, grade 3-6.7%, grade 4-1.4%). Grade 2 and above CRS was higher in non-malignant conditions (33% vs 13%, P-value .009). The percentage median rise in ferritin was 129%-grade 1, 171%-grade 2, and 344%-grade 3. Seven children received tocilizumab, and two of whom had ferritin values greater than 100 000 ng/mL with no mortality in this group. Low-dose adrenaline, high-flow nasal cannula, and ventilator support were needed in 13%, 10%, and 4%, respectively. Mortality in our cohort was 3/135 (2.2%), with two deaths due to sepsis and one due to grade 4 CRS. CONCLUSIONS: A risk-stratified approach using steroids in grade 2 and tocilizumab in grade 3/4 in the setting of haploSCT with NAC infusion and early use of low-dose adrenaline and HFNC can help provide adequate control of CRS, thereby ensuring optimal outcomes and survival.

Augmented immunosuppression and PTCY-based haploidentical hematopoietic stem cell transplantation for thalassemia major.

Alternate donor HSCT for thalassemia major from a matched unrelated donor or haploidentical family donor is a feasible therapeutic option in children with no matched family donor. Aggressive pretransplant immunosuppression, reduced toxicity conditioning, and PTCY result in excellent thalassemia-free survival. We describe here our experience in this cohort. We performed a retrospective analysis of the data on children who underwent a haploidentical HSCT for thalassemia major with PTCY at our center from August 2017 to August 2019. All children received pretransplant immune suppression for 6 weeks with fludarabine and dexamethasone, hypertransfusion and chelation with intravenous desferrioxamine. Conditioning included thiotepa, fludarabine, rabbit ATG, and cyclophosphamide, and GvHD prophylaxis included PTCY with tacrolimus. Twenty children were included and nineteen children engrafted. Acute hypertension occurred in five children, bacterial infection in eight children and viral respiratory infection in three children. Three children suffered from graft rejection. Reactivation of viruses namely CMV, adenovirus, and BK virus was seen in 60% of children. Grades 1-2 acute GvHD of the skin in four children (20%) and limited chronic GvHD of the skin in four children (20%). Immune cytopenia was documented in three children (15%). Haploidentical HSCT offers a therapeutic option for children with thalassemia major with no suitably matched family or unrelated donors. Our reduced toxicity regimen with PTCY offers a DFS of 75% and OS of 95% with low transplant-related mortality of 5%.

FLAG With Bortezomib in Childhood Relapsed/Refractory Leukemia: Remission Induction With Limited Toxicity in the Era of Multidrug-resistant Bacteria.

We present our experience on the use of fludarabine, cytarabine, granulocyte colony-stimulating factor in combination with Bortezomib. In total, 13 children with relapsed/refractory leukemia (acute lymphoblastic leukemia=9 and acute myeloid leukemia=4) were included from January 2018 to May 2019. Culture-positive sepsis and intensive care unit admission rates were 38% and 30%, respectively, with no postchemotherapy mortality in this cohort. Morphologic remission was documented in 92% and negative minimal residual disease was achieved in 61%, with 100% remission in those with acute myeloid leukemia. These results bear significant relevance in developing countries where multidrug-resistant sepsis is on the rise.

A Rare Cause of Rectovaginal Fistula in Early Infancy: It is in the Genes!

Acquired Rectovaginal Fistula (RVF) is rare in infants. Interleukin10/ Interleukin 10 receptor deficiencies are monogenic disorders presenting as aggressive forms of infantile onset inflammatory bowel disease with perianal abscess and fistula. Genetic studies assist in confirming the diagnosis. We present a two month old infant with rectovaginal fistula, severe colitis, failure to thrive and recurrent infections in whom colonoscopy revealed irregular colonic ulcers, and genetic studies confirmed an IL10RB mutation. Hematopoietic Stem cell transplantation is the definitive therapy for this disorder which the child underwent. We report this infant with an acquired RVF with extraintestinal features due to IL10RB mutation to highlight the importance of thinking beyond the local anatomy and looking into the genetic domain.

Matched Family versus Alternative Donor Hematopoietic Stem Cell Transplantation for Patients with Thalassemia Major: Experience from a Tertiary Referral Center in South India.

Hematopoietic stem cell transplantation (HSCT) is the only curative option available for patients with thalassemia major in India with increasing access to alternate donor transplantation for patients with no matched family donor. We aimed to analyze the impact of family and alternate donor HSCT on morbidity and mortality post-HSCT. We conducted a retrospective study in the department between July 2007 and December 2018 where all children who underwent HSCT for thalassemia major were included. A total of 264 children were included with a median age of 6 years (male/female, 1.4:1). The graft source was matched related donor (MRD) (76%; parent 15%, sibling 85%) and matched unrelated donor (MUD) (22%). All children received a myeloablative conditioning regimen with treosulfan/thiotepa/fludarabine in 93% and busulfan/cyclophosphamide in 7%. The source of stem cells was peripheral blood in 61%, bone marrow in 38%, and umbilical cord blood in 3%. The incidence of bacteremia was 14% versus 25% in MRD versus MUD groups. There was a higher incidence of posterior reversible encephalopathy syndrome (PRES) in the MUD group (10% versus 3%). Engraftment occurred in 97% with a higher trend toward mixed chimerism in the MRD group (12% versus 2%). When indicated, whole-blood donor lymphocyte infusion was used to ensure complete chimerism in children in the MRD group. A statistically significant difference was found in the incidence of graft versus host disease (GVHD), both acute and chronic between the MUD versus MRD groups, 60% versus 20% and 41% versus 17%, respectively (P = .001). Similarly, immune cytopenia and cytomegalovirus reactivation were also significantly higher in the MUD group, 27% versus 1.4% and 25% versus 2%, respectively (P = .001). Thalassemia-free survival in our cohort was 96%, 94%, and 84% with a median follow-up of 65 months in the matched sibling donor, matched family donor, and MUD groups, respectively. Overall survival of 95% and 90% with a median follow-up of 65 months was noted in those who underwent transplantation less than and greater than 7 years of age, respectively. MUD transplantation for patients with thalassemia major involves specific challenges such as PRES and unusual manifestations of GVHD such as immune cytopenia. Early interventions to optimize supportive care and measures to reduce GVHD are required to ensure survival rates of over 90%.

Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Fanconi Anemia: Improving Outcomes with Improved Supportive Care in India.

Fanconi anemia is the most common inherited bone marrow failure syndrome, and hematopoietic stem cell transplantation (HSCT) is the only curative option. Post-transplant cyclophosphamide (PTCy) is challenging in this group of children, given their increased sensitivity to chemotherapy. We performed a retrospective analysis of the data on children diagnosed with Fanconi anemia who underwent a haploidentical HSCT with PTCy from January 2014 to December 2019. Nineteen children (male/female, 0.75:1) underwent 21 haplo-HSCTs with PTCy. Fludarabine, low-dose cyclophosphamide, and 200 centi-gray total body irradiation were included in the conditioning regimen with 25 mg/kg PTCy on days +3 and +4. Haplo-graft was from a sibling in 38% and father in 57% of transplants. The source of stem cells was peripheral blood stem cells in 81% and bone marrow in 19% of transplants, with a median CD34 dose of 5.0 × 106/kg. We documented engraftment in 84% and primary graft failure in 10% of transplants. N-acetylcysteine (NAC) was infused concomitantly during cyclophosphamide in 13 children. Grade 2 and 3 mucositis was lower among those who received NAC as compared to those who did not (30% and 15% versus 33% and 50%), while transaminitis was higher among those who did not receive the infusion. The incidence of acute graft-versus-host disease (GVHD) was 68%, and 81% of these were steroid responsive (grade I/II). We documented chronic GVHD in 25% children, predominantly involving the skin and mouth, which responded to low-dose steroids and ruxolitinib. Serum ferritin was monitored twice weekly as a surrogate marker for cytokine release syndrome due to nonavailability of IL-6 levels. A 1- or 2-log increase in the titers of ferritin associated with clinical features guided the early addition of steroids in the periengraftment period. The mean survival was found to be less among those with high serum ferritin (>10,000 ng/dL) in the periengraftment period as compared to those with ferritin <10,000 ng/dL (mean survival of 25 ± 10 months versus 50 ± 6 months, respectively). The overall survival in our cohort was 68.4%, with a mean survival time of 41.5 months (95% confidence interval, 29.3 to 53.8 months), with a statistically significant correlation between inferior outcome and having received over 15 transfusions before HSCT (P = .01). PTCy can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of HSCTs. Focused interventions in this subset of children help improve survival outcomes. Early identification of cytokine release syndrome and risk-adapted steroid therapy during engraftment helps prevent mortality. The concomitant use of NAC during cyclophosphamide infusion helps reduce oxygen free radical related tissue damage and regimen-related toxicity.

Mendelian susceptibility to mycobacterial disease-Challenges in hematopoietic stem cell transplantation.

We present our experience in the hematopoietic stem cell transplantation (HSCT) in two children diagnosed with Mendelian susceptibility to mycobacterial diseases. The first child underwent a haploidentical HSCT with posttransplant cyclophosphamide using a reduced intensity conditioning following which he had primary graft failure. He was subsequently found to have interferon-γ1 receptor deficiency. He had immune reconstitution and is on antitubercular therapy. The second child diagnosed with IL12RB1 gene mutation underwent matched sibling donor HSCT with myeloablative conditioning following pretransplant immunosuppression with fludarabine and dexamethasone. He is 13 months post-HSCT with complete and remains disease free.

Treosulfan-based reduced toxicity hematopoietic stem cell transplantation in X-linked agammaglobulinemia: A cost-effective alternative to long-term immunoglobulin replacement in developing countries.

X-linked agammaglobulinemia (XLA) is a primary antibody disorder due to a mutation in the Bruton tyrosine kinase gene that requires lifelong immunoglobulin replacement resulting in a significant economic burden and treatment abandonment. Hematopoietic stem cell transplantation (HSCT) offers an alternative option for complete cure. In our series, two children with XLA underwent successful HSCT using a myeloablative conditioning with thiotepa, treosulfan, and fludarabine from a matched sibling donor. The second child had rejected his first graft following a busulfan-based regimen with resultant autologous reconstitution. At 6 months post-HSCT, serum IgG were normal, off IVIG, and had no infections. Both children after a median follow-up of 20 months have 100% chimerism. Treosulfan-based reduced toxicity myeloablative HSCT has encouraging results with a positive impact on the socioeconomics in developing countries.

Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide for Primary Immune Deficiency Disorders in Children: Challenges and Outcome from a Tertiary Care Center in South India.

Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Of the 16 transplants included in the study, 5 children were diagnosed to have Wiskott-Aldrich syndrome, 3 with congenital hemophagocytic lymphohistiocytosis, 2 each with Griscelli syndrome and Mendelian susceptibility to mycobacterial diseases, and one each with Chediak-Higashi syndrome, ORAI 1 mutation immune deficiency, severe combined immune deficiency, and Hyper IgM syndrome. The source of stem cells was PBSC in 62.5% and bone marrow in 32.5%. Engraftment by day 16-21 post hematopoietic stem cell transplantation was achieved in 75% transplants with 91% of these remaining in sustained complete chimerism. Acute skin and gut graft versus host disease of grade 2-3 were noted in 50% transplants and cytomegalovirus (CMV) reactivation in 43.7% transplants. One child with congenital HLH succumbed to refractory CMV, adenovirus, and BK virus infection. Cytokine release syndrome (CRS) was noted in 75% transplants with 2 children succumbing to the illness. Tocilizumab was successfully used early in one child. Overall mortality was found to be 37.5% with overall survival of 62.5% with a median follow-up of 23.3 months. In resource limited settings, PTCy has the potential to provide a cost-effective advantage in terms of accessibility of this curative procedure among children with PIDs.

Successful Treatment of Relapsed Isolated Extraocular Retinoblastoma in the Right Fibula With High-dose Chemotherapy and Autologous Stem Cell Transplantation.

Literature on high-dose chemotherapy followed by autologous stem cell rescue in relapsed retinoblastoma is limited to <150 cases reported so far. We present our experience and the challenges faced in the management of a 7-year-old boy with relapsed isolated extraocular retinoblastoma in the right fibula who received salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell rescue. Electrolyte disturbances, renal tubulopathy, and seizures were the most significant transplant-related morbidity. The child is now 3 years postautograft in remission. Monitoring for second malignant neoplasm and late side effects remain the main challenges in the years to come.

Excellent remission rates with limited toxicity in relapsed/refractory Langerhans cell histiocytosis with pulse dexamethasone and lenalidomide in children.

Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. We used a novel protocol including six cycles of pulse dexamethasone and lenalidomide in four children with LCH refractory to first-line agents and courses of cladribine and cytarabine or single-agent cladribine. All four children completed the protocol without any significant adverse effects and remain in complete and durable remission 15-18 months posttreatment. The novel protocol we propose for relapsed/refractory LCH is cost-effective and outpatient-based with durable remission and minimal toxicity. This is particularly suited for resource-limited settings.

Combating blood stream infections during induction chemotherapy in children with acute myeloid leukemia: Single center results in India.

Optimal management of infectious complication is the biggest challenge in children receiving chemotherapy for acute myeloid leukemia (AML). We have analyzed the data of children undergoing AML induction chemotherapy at our center from 2002 to 2016 and found that Gram-negative infections are more predominant when compared to the published literature. There also has been a surge in multidrug-resistant (MDR) infections over the last 4 years, which has increased the need for supportive care and escalated the cost of care. We have introduced certain novel methods to combat MDR sepsis and decrease mortality rates.

Cytomegalovirus reactivation posthematopoietic stem cell transplantation (HSCT) and type of graft: A step toward rationalizing CMV testing and positively impacting the economics of HSCT in developing countries.

We aimed to determine a correlation between cytomegalovirus reactivation post hematopoeitic stem cell transplantation (post-HSCT) with the type of graft source, defining children at risk. We analyzed data on children less than 18 years of age undergoing HSCT from 2002 to May 2016 (n = 464). Correlation between reactivation and graft source was analyzed statistically. Reactivation occurred in 3% of children with matched-related donor (MRD) transplants, 33.3% with unrelated peripheral blood stem cells, 17.4% with unrelated cords, and 36.5% (15/41) with mismatched or haploidentical grafts (P = <0.0001). MRD does not warrant weekly PCR, unlike unrelated or haploidentical donors, thus defining protocols for developing countries with limited resources.