ABSTRACT
We studied the incidence of relapse, transformation to myelodysplastic syndrome/acute myeloid leukemia, and survival in patients with aplastic anemia (AA) surviving more than 1 year after ATG/ALG-based immunosuppressive therapy (IST) between 1985 and 2020. Four-hundred seventy patients (413 adults and 57 children) were studied, and data were compared with 223 patients who underwent matched sibling donor transplant (MSD HSCT). Median follow-up is 50 months (12-359). Relapse occurred in 21.9% at a median time of 33.5 months (5-228) post IST. Twenty-six (5.5%) patients progressed to PNH, while 20 (4.3%) evolved to MDS/AML. Ten-year estimated overall survival (OS) is 80.9 ± 3% and was significantly better in patients without an event (85.1 ± 4%) compared to relapse (74.6% ± 6.2%) or clonal evolution (12.8% ± 11.8%) (p = 0.024). While the severity of AA (p = 0.011) and type of ATG (p = 0.028) used predicted relapse, only age at IST administration influenced clonal evolution (p = 0.018). Among HSCT recipients, relapse rates were 4.9% with no clonal evolution, and the 10-year OS was 94.5 ± 2%. In patients who survived 1 year following IST, outcomes were good except with clonal evolution to MDS/AML. These outcomes, however, were still inferior compared to matched sibling donor HSCT.
Subject(s)
Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Adult , Child , Humans , Graft vs Host Disease/etiology , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Immunosuppression Therapy/adverse effects , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/complications , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , RecurrenceABSTRACT
INTRODUCTION: Total marrow lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increasing toxicity compared to Total body irradiation (TBI). METHODS: Twenty adult patients undergoing hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia with lymphoid blast crises (CML-LBC) received TMLI and cyclophosphamide for conditioning. Ten patients each received 13.5 or 15 Gy of TMLI. The graft source was peripheral blood stem cells in all, and donors included matched related (n = 15), haplo-identical (n = 3) or matched unrelated donors (n = 2). RESULTS: The median cell dose infused was 9 × 106 CD34/kg (range 4.8-12.4). Engraftment occurred in all (100%) at a median of 15 days (range: 14-17). Toxicity was low with hemorrhagic cystitis seen in two but no sinusoidal obstruction syndrome. Acute GVHD occurred in 40% while chronic GVHD was seen in 70.5%. Viral infections were seen in 55% while blood stream bacterial infections occurred in 20% and invasive fungal disease (IFD) in 10%. The Day 100 non-relapse mortality (NRM) was 10%. At a median follow up of 25 months (range 2-48), two patients have relapsed. Overall survival at 2 years is 80% while the disease-free survival is 75%. CONCLUSIONS: The combination of TMLI and cyclophosphamide for myeloablative conditioning is associated with low toxicity and favorable early outcomes in patients undergoing HSCT for ALL and CML-LBC.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Bone Marrow/radiation effects , Blast Crisis , Lymphatic Irradiation , Cyclophosphamide/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Graft vs Host Disease/etiology , Chronic Disease , Transplantation Conditioning/adverse effects , Leukemia, Myeloid, Acute/etiology , Retrospective StudiesABSTRACT
Although telomere shortening is seen frequently in patients with aplastic anaemia (AA), there are no data on its association in matched sibling donor (MSD) transplants. We evaluated the effect of pre-transplant telomere length of patients and donors, measured by quantitative real-time polymerase chain reaction in 163 recipients undergoing MSD transplants. The median age of patients and donors was 24 and 26 years, respectively. Fludarabine and cyclophosphamide was the main conditioning regimen used and all received peripheral blood stem cell grafts. Engraftment occurred in 89% with graft failure (primary and secondary) in 6%. Acute and chronic graft-versus-host disease (GVHD) occurred in 28% and 24%, respectively. At a median follow-up of 37 months, 117 patients (72%) were alive. All patients and donors were divided into short and long telomere length based on their median and quartile values. Patient telomere length was not associated with severity of AA, neutrophil recovery, graft failure, acute GVHD or chronic GVHD. Longer donor telomere length was associated with better overall survival [hazard ratio (HR) = 0·2, P = 0·006] but did not influence neutrophil recovery, graft failure, acute or chronic GVHD. The five-year overall survival was significantly better (94·9 ± 3·5% vs 65·4 ± 4·3%, P = 0·002) for donors with long (highest quartile, DTL-HQ) versus short (lower three quartiles, DTL-LQ) telomeres, respectively. On multivariate analysis, longer donor telomere length, recipient age and acute GVHD continued to remain significant. This is the first study demonstrating an association of donor telomere length on overall survival following MSD transplant for AA but it needs to be confirmed in larger studies.
Subject(s)
Anemia, Aplastic/mortality , Anemia, Aplastic/therapy , Hematopoietic Stem Cell Transplantation , Siblings , Telomere Homeostasis , Telomere/genetics , Tissue Donors , Adolescent , Adult , Age Factors , Child , Child, Preschool , Female , Graft Rejection , Graft Survival , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Middle Aged , Prognosis , Transplantation Conditioning/methods , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Splenectomies though well-established in the successful management of several resistant haemoglobinopathies, have not been studied in detail in the paediatric population to assess the outcomes. We conducted this review to primarily assess the surgical and anaesthetic outcomes of paediatric splenectomies and secondarily highlight factors predictive for a high-risk splenectomy. METHODS: A 5 year retrospective chart review was made, and patient follow-up was done jointly using the hospital electronic medical records and telephonic calls. A p value of < 0.05 was considered significant. RESULTS: Among the 69 splenectomised children, 61% were male and the overall mean age was 10.2 years. The cohort consisted of patients with thalassemia (46%), ITP (30%), haemolytic anemia (19%) and 1 child each with lymphoma, splenic cyst and Kassabach Meritt syndrome. Most (96%) were electively operated and 23% were performed laparoscopically. 61% received intravenous analgesia and the mean volume of fluid administered intra-operatively was 21 ml/kg. There was no documented OPSI, and there was one mortality. The mean follow-up period was 43 months and the overall survival rate was 98.5%. CONCLUSIONS: Splenectomy was associated with a promising overall outcome. A greater pre-operative transfusion requirement, a larger sized spleen and increased fluid administration intra-operatively, were associated with a worse outcome.
Subject(s)
Analgesia , Anesthetics , Laparoscopy , Child , Female , Humans , Male , Retrospective Studies , Splenectomy , Tertiary HealthcareABSTRACT
The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)-based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4·5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55·6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90·3 (5·3)% versus 58·6 (10·4)% (P = 0·004), and 87·1 (6·0)% versus 47·7 (10·3)% (P = 0·001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4·91, 95% confidence interval (CI) 1·56-15·41; P = 0·006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent long-term survival.
Subject(s)
Antineoplastic Agents/therapeutic use , Arsenic Trioxide/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adolescent , Adult , Child , Child, Preschool , Disease Management , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Salvage Therapy , Treatment Outcome , Young AdultABSTRACT
The use of cytokine mobilized peripheral blood stem cells (PBSC) for stem cell transplantation offers early engraftment, and less early transplant related mortality and morbidity. This can be done easily in the out-patient setting in an adult donor, but is difficult in children. The safety and efficacy of general anaesthesia outside the controlled operation room setting is quite challenging and demanding. We present our experience with paediatric PBSC harvest done under anaesthesia in the out-patient setting between January 2009 to June 2017. A total of 158 children underwent 164 PBSC harvests during the study period. Donors were predominantly females with a median age of 5 years (1-12) and a median weight of 17.5â¯kg (9.4-51). In 50% of the cases, induction of anaesthesia was by sevoflurane followed by total intravenous anaesthesia (TIVA) while in 32% it was sevoflurane induction followed by sedation. Hudson mask (48.5%) and laryngeal mask airway (50%) were the most common modes of airway and all patients were ventilated in the spontaneous mode. Propofol was the most commonly used maintenance agent (67%). There were no major complications except for acute pulmonary edema secondary to infusion of blood products requiring a short stay in ICU for one donor. All donors were discharged on the next day of harvest. No long term complications have been reported in any of these donors. Paediatric PBSC harvest can be safely done under anaesthesia with due precautions in the day care setting.
Subject(s)
Anesthesia/methods , Peripheral Blood Stem Cell Transplantation/methods , Peripheral Blood Stem Cells/metabolism , Child, Preschool , Day Care, Medical , Female , Humans , MaleABSTRACT
OBJECTIVES: To study the clinical profile and outcomes of patients with paraproteinemic neuropathy (PPN) and to explore the utility of nerve conduction studies (NCSs) to differentiate between the demyelinating subtypes. METHODS: We did a retrospective analysis of patients diagnosed with PPN between January 2010 and December 2019 in an inpatient setting. The study population consisted of patients above 16 years of age presenting with clinical features suggestive of chronic peripheral neuropathy and on evaluation was found to have PPN. RESULTS: A total of 74 patients were identified. The patients were predominantly in the 6th decade, and the majority were males. The subtypes of PPN were monoclonal gammopathy of undetermined significance (MGUS) (45.9%), POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) (24.3%), solitary plasmacytoma (17.6%), multiple myeloma (8.1%), and AL amyloidosis (4.1%). There are specific features on NCS which can help in identifying POEMS syndrome and IgM MGUS. The majority of patients with PPN tend to stabilize or improve with treatment; however, many have a severe residual disability. New terminology and classification of these entities as 'monoclonal gammopathies of neurological significance' can aid in early diagnosis and the development of effective treatment, to prevent residual disability. CONCLUSION: PPN has a heterogeneous spectrum of clinical, biochemical, and electrophysiological features. NCS can help distinguish POEMS syndrome and IgM MGUS from other demyelinating subtypes.
Subject(s)
Monoclonal Gammopathy of Undetermined Significance , Paraproteinemias , Peripheral Nervous System Diseases , Plasmacytoma , Humans , Male , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Paraproteinemias/complications , Paraproteinemias/diagnosis , Retrospective StudiesABSTRACT
The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have ensured increased longevity in transplant recipients. However, they do have late effects that may adversely affect the endocrine system, bone health, and body composition. This study was undertaken to evaluate bone mineral density (BMD), trabecular bone score, and body composition in recipients of allo-HSCT and compare them with age, sex, and body mass index (BMI) matched controls. This was a cross-sectional study done in 63 cases and 65 matched controls. The mean femoral neck BMD was found to be lower in cases than in controls (0.777 [0.119] versus 0.846 [0.122] g/cm2, P = .002). Among cases, the mean BMD at the neck of femur was lower in patients who had received myeloablative conditioning compared with those who had received the nonmyeloablative regimen (0.731 [0.090] versus 0.802 [0.126] g/cm2, P = .014]. The mean (SD) bone density at the lumbar spine was significantly lower in the group that had received total body irradiation compared with the group that did not (0.930 [0.111] versus 0.993 [0.127], P = .044). Trabecular bone score did not differ between cases and controls (1.383 [0.877] versus 1.389 [0.750], P = .670). The lean mass was significantly lower (15.9 [2.4] versus 18.6 [4.8] kg/m2, P < .001) and the prevalence of sarcopenia (42% versus 11%, P < .001) significantly higher in cases than in controls. Normal-weight obesity was also noted to be higher among those with sarcopenia than in those without (12/26 versus 5/36; P = .009). The procedure of allo-HSCT may thus cause an impairment of bone health and alterations in body composition well after the cure of the primary disease.
Subject(s)
Bone Density , Hematopoietic Stem Cell Transplantation , Body Composition , Cross-Sectional Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , IndiaABSTRACT
Treatment of Hodgkin lymphoma (HL) has evolved with risk-stratified therapy based on PET-CT scan at multiple timepoints. In a resource constraint setting even a single PET-CT scan ($400) is inaccessible to many patients, who are re-assessed with only clinical examination, abdominal ultrasonogram and/or x-ray (C/U/X) ($10). To compare clinical outcomes in patients with HL who have had suboptimal imaging after completion of chemotherapy for HL, with those who had a CT or PET-CT, 283 patients were treated for HL from 2011 to 2015, and 268 patients completed six cycles of ABVD therapy with response assessment modality by CT/PET in 185 patients and by C/U/X in 83. There was no difference in the number of patients with advanced (64·1% vs. 61·1%; P = 0·650) or bulk disease (8·1% vs. 7·2%). A significantly higher number of patients in the CT/PET group received IFRT (25·4% vs. 7·7%; P = 0·0005). The three-year overall survival and progression-free survival of all treated patients (n = 283) was 83·5 ± 2·3% and 76·7 ± 2·6% respectively [median follow-up 36 months (range 2-93)]. At three years, the overall relapse-free survival (RFS) was 80·1 ± 2·5%, with RFS of 77 ± 3·2% vs. 85 ± 4·0% in the CT/PET group and C/U/X groups respectively (P = 0·349). There was no difference in RFS between the two groups either in early-stage disease (88·1 ± 4·6% vs. 91·8 ± 5·6%; P = 0·671) or late-stage disease (73·9 ± 4·8% vs. 81·3 ± 6·0%; P = 0·747). The only significant factor adversely affecting RFS was advanced disease (P = 0·004). Factors not affecting RFS were age (P = 0·763), sex (P = 0·925), bulk disease (P = 0·889) and imaging modality (P = 0·352). There was no difference in relapse rates between patients who had suboptimal imaging compared to those who had a PET/CT. It is possible to use these basic imaging modalities when resources are a constraint, with acceptable outcomes.
Subject(s)
Hodgkin Disease/diagnostic imaging , Adult , Female , Hodgkin Disease/pathology , Humans , Male , Retrospective StudiesABSTRACT
Arsenic trioxide (ATO)-based regimens are the standard of care for treating acute promyelocytic leukaemia (APL) and have replaced chemotherapy-based approaches. However, the cost of "patented" ATO is prohibitive because of patent rights. "Generic" ATO has been used in a few countries, but its implications for health resource utilization (HRU) and cost of treatment are unknown. We hypothesized that treating APL patients using generic ATO (APL-ATO) will be cost effective compared to the chemotherapy-based regimen (APL-CT). In a single-centre retrospective study, we used a bottom-up costing method to compare the direct medical cost of treatment and HRU between APL-ATO and APL-CT. These costs and the survival and relapse probabilities were imputed in a three-state Markov decision model to estimate the cost effectiveness of APL-ATO compared to APL-CT. The mean cost of treatment for APL-ATO (n = 30, $8500 ± 2078) was significantly less than for APL-CT (n = 30, $22 600 ± 5528) (P < 0·001). APL-ATO reduced hospitalization, antibiotic and antifungal usage (P < 0·001). In the Markov model, five-year treatment costs were significantly lower for APL-ATO ($11 131) than for APL-CT ($17 926) (P < 0·001). Treatment cost and health resource utilization were significantly lower for generic ATO-treated APL patients compared to the chemotherapy-based regimen.
Subject(s)
Antineoplastic Agents/therapeutic use , Arsenic Trioxide/therapeutic use , Cost-Benefit Analysis/methods , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/economics , Adult , Antineoplastic Agents/pharmacology , Arsenic Trioxide/pharmacology , Humans , Retrospective StudiesABSTRACT
BACKGROUND: With the increasing incidence of multidrug-resistant (MDR) organisms and high mortality rates associated with these infections, we describe the spectrum of the major drug-resistant pathogens identified in fecal surveillance, and re-visit the use of fecal surveillance in predicting infection with these organisms post-allogeneic stem cell transplant. METHODS: Data from allogeneic stem cell transplant recipients with common drug-resistant strains of bacteria in fecal surveillance (Escherichia coli, Klebsiella spp., and Enterococcus spp.) were compared with recipients who did not have the same in fecal surveillance cultures. Baseline characteristics and post-transplant outcomes including similar drug resistance in blood cultures, severe sepsis, and 100-day transplant-related mortality were compared. Multivariate analysis using logistic regression model was used to determine independent predictors of outcome. RESULTS: In 232 transplants, the prevalence of common drug-resistant isolates in fecal surveillance cultures was 57.7% (134 out of 232 patients-with a single isolate in 115 and ≥2 isolates in the remaining 19 patients. A total of 164 drug-resistant isolates were obtained from 134 patients. Of the 164 isolates, 133 (81%) were positive for ESBL screening, 19 (11.5%) for carbapenem-resistant organisms (CRO) screening, 12 (7.3%) for VRE screening. Patients who had common drug-resistant pathogens detected in fecal surveillance have significantly higher subsequent blood culture positivity with drug resistance, as well as higher 100-day mortality. Factors influencing 100-day mortality included patient's age (P = .001), drug resistance positivity in blood (P < .001), drug resistance in fecal surveillance (P = .011), use of an alternate donor (other than fully matched sibling) (P < .001), GVHD grade 3-4 (P < .001), and severe sepsis (P < .001). On multivariate analysis, only use of an alternate donor (0.024), severe sepsis (P < .001), and grade 3-4 GVHD (P < .001) retained significance in predicting 100-day mortality. CONCLUSION: Organisms resistant to 3rd generation cephalosporins are frequently seen on fecal surveillance in the pre-transplant setting and are associated with a higher incidence of drug-resistant organisms in subsequent blood cultures (not limited to the same drug resistance pattern as seen in fecal surveillance). Drug-resistant organisms in fecal surveillance are associated with poorer outcomes following allogeneic stem cell transplant and may be used as a guide to identify patients at risk of subsequently developing a drug-resistant organism in blood.
Subject(s)
Bacteremia/diagnosis , Bacteria/drug effects , Drug Resistance, Multiple, Bacterial , Feces/microbiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Adult , Bacteremia/mortality , Bacteria/classification , Bacteria/isolation & purification , Child , Child, Preschool , Diagnostic Screening Programs , Female , Humans , Infant , Male , Middle Aged , Outcome and Process Assessment, Health Care , Retrospective Studies , Sepsis/etiology , Sepsis/mortality , Young AdultABSTRACT
Graft rejection (GR) after allogeneic stem cell transplantation (allo-SCT) occurs in 10% to 20% of patients with ß-thalassemia major (TM). There are limited data on the clinical profile and long-term outcome of patients who have had a GR. We undertook a retrospective analysis of patients who had a graft failure after allo-SCT for TM at our center. From October 1991 to June 2016, 55 of 506 patients (11%) transplanted for TM had a graft failure. An additional 7 patients with graft failure after allo-SCT done at other centers were referred to us for a second transplant. The median age was 8 years (range, 1 to 19), and there were 38 males (61.2%). Thirty-two patients (52.4%) were primary graft failures (15 with aplasia and 17 with autologous recovery) and 30 (47.6%) were secondary graft failures (5 with aplasia and 25 with autologous recovery). On conventional risk stratification 40 patients (64.5%) were class III. Seventeen patients (53.12%) with primary graft failure and 16 (53.3%) with secondary graft failure did not receive a second transplant. Twenty-nine patients (46%) with GR underwent a second allo-SCT. With the exception of 1 patient (first allo-SCT with an unrelated cord blood product), the donor for the second transplant was the same as the first transplant. Conditioning regimen for the second SCT was busulfan-based myeloablative (MAC) in 7 patients (24%), treosulfan-based MAC in 12 patients (41.3%), and the remaining received non-MAC regimens in view of pancytopenia and perceived inability to tolerate MAC. None of the patients conditioned with a treosulfan-based regimen had a GR, although 1 patient died with complications secondary to chronic graft-versus-host disease. Of the remaining 17 patients, 10 died after the second GR and 3 of regimen-related toxicity. Four are alive, of which 1 has recurrent TM and the rest are well and transfusion independent at 55, 80, and 204 months, respectively, from second transplant (all busulfan-based MAC). On a univariate analysis a nontreosulfan-based conditioning regimen and time from GR to second transplant of <1 year was significantly associated with an adverse impact. However, on a multivariate analysis only a nontreosulfan-based regimen was associated with a significant adverse impact on event-free survival (HR, 11.5; 95% CI, 1.13 to 116.4; P = .039). In conclusion, there has been a significant improvement in clinical outcomes in our experience with the use of a treosulfan-based reduced-toxicity MAC regimen for second allo-SCT for TM. It would be reasonable, where feasible, to defer the second transplant by a year after the first GR.
Subject(s)
Busulfan/analogs & derivatives , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , beta-Thalassemia/therapy , Adolescent , Busulfan/therapeutic use , Child , Child, Preschool , Female , Graft Rejection , Hematopoietic Stem Cell Transplantation/mortality , Humans , Infant , Male , Reoperation , Transplantation Conditioning/mortality , Treatment Outcome , Young Adult , beta-Thalassemia/mortalityABSTRACT
High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m2 [MTX15] and 10 mg/m2 [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.
Subject(s)
Anemia, Aplastic/therapy , Cyclophosphamide/administration & dosage , Graft vs Host Disease/prevention & control , Peripheral Blood Stem Cell Transplantation , Acute Disease , Adolescent , Adult , Allografts , Anemia, Aplastic/mortality , Chronic Disease , Female , Graft vs Host Disease/mortality , Humans , Male , Middle AgedABSTRACT
Autologous transplantation is the standard of care for transplant-eligible patients with multiple myeloma. Toward making this treatment accessible in developing countries, there are significant challenges like resource constraints and access to cryopreservation facilities. We performed a retrospective analysis of patients with multiple myeloma who underwent autologous transplantation using granulocyte colony-stimulating factor (G-CSF)-mobilized non-cryopreserved grafts at our institution from January 1995 to December 2014. Peripheral blood stem cells (PBSCs) were harvested over 1 to 2 days after G-CSF mobilization. After apheresis, PBSCs were stored at 4°C in a blood bank refrigerator for up to 72 hours. During the study period, 224 patients with multiple myeloma underwent autologous transplantation using G-CSF-mobilized non-cryopreserved grafts. The number of days of stem cell harvest was 1 in 91 patients (40.6%) and 2 in 133 patients (59.4%). The median CD34 cell dose was 4.87â¯×â¯106/kg (range, 1.15 to 23.7). All patients except 1 engrafted. The median time to neutrophil engraftment was 12 days (range, 9 to 22). The median time to platelet engraftment was 17 days (range, 10 to 44). In a resource-limited setting, the use of G-CSF-mobilized non-cryopreserved grafts results in adequate engraftment for most patients with multiple myeloma undergoing autologous stem cell transplantation.
Subject(s)
Multiple Myeloma/surgery , Multiple Myeloma/therapy , Peripheral Blood Stem Cells/metabolism , Transplantation, Autologous/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Multiple Myeloma/pathology , Retrospective Studies , Young AdultSubject(s)
Anemia, Hemolytic, Autoimmune/etiology , COVID-19/complications , Purpura, Thrombocytopenic, Idiopathic/etiology , Thrombocytopenia/etiology , Adult , Anemia, Hemolytic, Autoimmune/blood , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Dexamethasone/administration & dosage , Humans , Male , Middle Aged , Platelet Count , Platelet Transfusion , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/therapy , SARS-CoV-2 , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/therapy , Treatment OutcomeABSTRACT
The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.
Subject(s)
Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Purpura, Thrombocytopenic, Idiopathic/surgery , Splenectomy/methods , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Disease-Free Survival , Female , Follow-Up Studies , Hemorrhage/etiology , Hemorrhage/mortality , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/mortality , Proportional Hazards Models , Purpura, Thrombocytopenic, Idiopathic/pathology , Retrospective Studies , Sepsis/etiology , Sepsis/mortality , Splenectomy/adverse effects , Survival Rate , Time Factors , Young AdultABSTRACT
Treatment options have expanded rapidly and widely in the past two decades for patients with multiple myeloma. Triplet novel agent-based induction regimens have been accepted as the standard practice wordwide over the last decade both for transplant-eligible and non-eligible patients. The addition of anti-CD38 monoclonal antibodies as part of quadruplet regimens has led to even deeper and longer-lasting responses. The impressive results shown by the quadruplets havebeen practice-changing where accessible in recent years. Chimeric antigen receptor T cell therapy and bispecific antibodies are being tested in the upfront setting and have the potential to once again shift the paradigm of treatment of newly diagnosed MM.
Subject(s)
Antineoplastic Agents , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/therapy , Antineoplastic Agents/therapeutic use , Immunotherapy, AdoptiveABSTRACT
Osteopetrosis is a clinically and genetically heterogeneous group of inherited bone disorders that is caused by defects in osteoclast formation or function. Treatment options vary with the disease severity and an accurate molecular diagnosis helps in prognostication and treatment decisions. We investigated the genetic causes of osteopetrosis in 31 unrelated patients of Indian origin. Screening for the genetic variants was done by Sanger sequencing or next generation sequencing in 48 samples that included 31 samples from index patients, 16 from parents' and 1 chorionic villus sample. A total of 30 variants, including 29 unique variants, were identified in 26 of the 31 patients in the study. TCIRG1 was the most involved gene (n = 14) followed by TNFRSF11A (n = 4) and CLCN7 (n = 3). A total of 17 novel variants were identified. Prenatal diagnosis was done in one family and the foetus showed homozygous c.807 + 2T > G variant in TCIRG1. Molecular diagnosis of osteopetrosis aids in therapeutic decisions including the need for a stem cell transplantation and gives a possible option of performing prenatal diagnosis in affected families. Further studies would help in understanding the genetic etiology in patients where no variants were identified. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01732-4.
ABSTRACT
Haplo-identical stem cell transplant using post-transplant cyclophosphamide is increasingly being used in children without a matched sibling donor. Between 2010 and June 2021, 127 children underwent 138 transplants with a median age of 7.1 years for malignant and non-malignant disorders. Conditioning regimens included both myeloablative and reduced intensity regimens with peripheral blood stem cells as the main graft source. Engraftment occurred in 113 [81.9%] at a median of 16 days [range: 10-32] with primary graft failure in 10.2%. Cumulative incidence of grade II-IV acute graft versus host disease (GVHD) was 49.5% and chronic GVHD in 40.7%. Majority [92.7%] had at least one infection with 31% incidence of bacterial infection, 76% incidence of viral and 16% incidence of fungal infection. The 2-year overall survival (OS) is 54.9 ± 4.6% with a lower survival among young children aged 0-5 years [28.2 ± 6.4%] compared to 5-10 years [71.3 ± 6.8%] and 11-15 years [55.7 ± 8.8%] [p = 0.032]. 2-year OS has gradually improved from 25.0 ± 2.1% for 2010-2013 to 47.5 ± 6.2% for 2014-2017 and 67.1 ± 6.6% for 2018-2021 [p = 0.049]. On multivariate analysis, bacterial infection [p = 0.017], invasive fungal disease [p = 0.002] and graft failure [p = 0.029] negatively impacted overall survival. Haplo-identical SCT with post-transplant cyclophosphamide is a reasonable option for children who do not have a matched sibling donor. Strategies to reduce graft failure, infection related mortality and GVHD needs to be explored.
ABSTRACT
A toxicity-reduced conditioning regimen with treosulfan, fludarabine, and thiotepa in patients with high-risk ß-thalassemia major has significantly improved hematopoietic stem cell transplantation (HCT) outcomes. However, complications resulting from regimen-related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose-exposure-response relationship of treosulfan and its active metabolite S, S-EBDM, in a uniform cohort of patients with ß-thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of treosulfan is feasible. Plasma treosulfan/S, S-EBDM levels were measured in 77 patients using a validated liquid chromatography with tandem mass spectrometry method, and the pharmacokinetic parameters were estimated using nlmixr2. The influence of treosulfan and S, S-EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1-year overall survival (OS), and thalassemia-free survival (TFS) were assessed. We observed that treosulfan exposure was lower in patients with graft rejection than those without (1,655 vs. 2,037 mgâ¢h/L, P = 0.07). Pharmacodynamic modeling analysis to identify therapeutic cutoff revealed that treosulfan exposure ≥1,660 mgâ¢hour/L was significantly associated with better 1-year TFS (97% vs. 81%, P = 0.02) and a trend to better 1-year OS (90% vs. 69%, P = 0.07). Further, multivariate analysis adjusting for known pre-HCT risk factors also revealed treosulfan exposure <1,660 mgâ¢h/L (hazard ratio (HR) = 3.23; 95% confidence interval (CI) = 1.12-9.34; P = 0.03) and GSTA1*B variant genotype (HR = 3.75; 95% CI = 1.04-13.47; P = 0.04) to be independent predictors for inferior 1-year TFS. We conclude that lower treosulfan exposure increases the risk of graft rejection and early transplant-related mortality affecting TFS. As no RRTs were observed with increasing treosulfan exposure, TDM-based dose adjustment could be feasible and beneficial.