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Clinical Lymphoma, Myeloma & Leukemia May 2024No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and...
BACKGROUND
No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence.
OBJECTIVE
To evaluate efficacy and safety of standard dose (200 mg/m = Mel200) versus reduced dose 140 mg/m = Mel140) of melphalan in patients with MM undergoing ASCT.
DESIGN
A single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS). Secondary safety and efficacy endpoints included overall survival (OS), incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age and renal function.
RESULTS
A total of 322 patients were included in the study, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar except patients receiving Mel140 were on average older and had worse kidney function. PFS at 2 years was not different between groups (P = .2335). No difference existed in 2 year PFS or OS for patients < 65 years of age versus ≥ 65 years of age or for patients with CrCl 30-59 mL/min versus CrCl ≥ 60 mL/min within either Mel200 group or Mel140 group (all P > .05). No differences existed between groups across all secondary outcomes.
CONCLUSION
Reduced doses melphalan showed no differences in safety or efficacy outcomes versus standard dose even when analyzed based on age and renal function. Larger randomized controlled trials need to be performed to validate these findings.
PubMed: 38845275
DOI: 10.1016/j.clml.2024.05.005 -
Blood Advances Jun 2024Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is...
Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is used as a consolidation strategy after achieving clinical remission with first-line therapy, as well as in chemosensitive relapse if allogeneic transplant is not an option. CD25 is a targetable protein often highly expressed in PTCL. In this phase 1 clinical trial, we tested the addition of beta-emitting 90Y-labeled chimeric anti-CD25 basiliximab (aTac) to BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning for AHCT in patients with PTCL. Twenty-three AHCT-eligible patients were enrolled, and 20 received therapeutic 90Y-aTac-BEAM AHCT. Radiation doses of 0.4, 0.5 and 0.6 mCi/kg were tested. With no observed dose-limiting toxicities, 0.6 mCi/kg was deemed the recommended phase 2 dose. The most prevalent adverse effect, grade 2 mucositis, was experienced by 80% of patients. As of this report, 6 (30%) of the treated patients had died, 5 due to progressive disease and 1 due to multiple organ failure [median time of death 17 mo (range: 9-21 mo)] post-AHCT. Median follow-up was 24 mo (range: 9-26 mo) overall and 24 mo (range: 13-26 mo) for surviving patients. For patients who received therapeutic 90Y-aTac-BEAM AHCT, the 2-year progression-free and overall survival were 59% (95% CI: 34-77%) and 68% (95% CI: 42-84%), respectively. 90Y-aTac-BEAM appears to be safe as an AHCT conditioning regimen for PTCL, with no increased toxicity over the toxicities historically seen with BEAM alone in this patient population. This trial was registered at www.clinicaltrials.gov as # NCT02342782.
PubMed: 38838232
DOI: 10.1182/bloodadvances.2023012497 -
American Journal of Hematology Jun 2024
PubMed: 38837272
DOI: 10.1002/ajh.27406 -
Japanese Journal of Ophthalmology Jun 2024To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber.
PURPOSE
To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber.
STUDY DESIGN
Retrospective analysis.
METHODS AND PATIENTS
This study was sanctioned by theNational Cancer Center Hospital' Independent Ethics Committee. The surgeon was a general interventional radiologist. After confirming that the distal internal carotid artery was not delineated by balloon occlusion and the ophthalmic artery was visualized using digital subtraction angiography, melphalan was manually administered. Notably, in cases presenting bilateral retinoblastoma, both eyes received treatment in a singular, low-dose procedure. Between July 2015 and December 2021, 125 patients with retinoblastoma (68 boys and 57 girls) underwent SOAI at our facility. The average age at initial treatment was 19.3 months. The study covered 250 procedures, with patients undergoing an average of 3.7 procedures.
RESULTS
The success rate of the procedure was 99.2%, with a mean procedure duration of 18.3 min. Two distinct technical failures were recorded: one attributed to an internal carotid artery having a wide lumen and the other due to the ophthalmic artery remaining undetected on angiography post-balloon occlusion of the internal carotid artery. Adverse events were minimal but included bronchospasm post-procedure and severe orbital inflammation in 0.8% and 0.4% of cases, respectively.
CONCLUSION
SOAI using the microballoon catheter with the M chamber is a feasible and safe procedure for the treatment of retinoblastoma. The success rate was 99.2%. This system can be recommended as intra-arterial chemotherapy for retinoblastoma.
PubMed: 38833074
DOI: 10.1007/s10384-024-01067-1 -
British Journal of Haematology Jun 2024For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative...
For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative treatment option. Early response to treatment during conditioning indicates chemotherapy-responsive disease and may have prognostic value. We retrospectively evaluated blast clearance on day 5 after melphalan, administered 11 days prior to alloSCT as part of a sequential conditioning in 176 patients with active AML. Overall survival (OS) was 52% (95% confidence interval [CI] 45%-60%), and relapse-free survival (RFS) was 47% (95% CI 40%-55%) at 3 years. Patients who achieved early blast clearance did not show a significant improvement in OS and RFS (OS, hazard ratio [HR] HR 0.75, p 0.19; RFS, HR 0.71, p 0.09, respectively), but had a significantly lower non-relapse mortality rate (HR 0.46, p 0.017). HLA-mismatched donor, older age, adverse genetic risk and higher comorbidity scores were associated with inferior survival outcomes. A high initial blast count was only associated with inferior prognosis in patients receiving chemotherapy-only compared to total body irradiation containing conditioning therapy. These results indicate that for patients transplanted with active AML, sensitivity to chemotherapy might be of less importance, compared to other disease- and transplant-related factors.
PubMed: 38831752
DOI: 10.1111/bjh.19552 -
Journal of Pediatric Hematology/oncology Jul 2024The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate....
BACKGROUND
The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma.
METHODS
We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen.
RESULTS
We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy.
CONCLUSION
This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.
Topics: Humans; Hepatoblastoma; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Male; Female; Child, Preschool; Liver Neoplasms; Neoplasm Recurrence, Local; Transplantation, Autologous; Child; Infant; Antineoplastic Combined Chemotherapy Protocols; Survival Rate; Salvage Therapy; Transplantation Conditioning; Carboplatin; Prognosis
PubMed: 38830616
DOI: 10.1097/MPH.0000000000002888 -
BioRxiv : the Preprint Server For... May 2024Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the...
Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such as and . Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such as and . Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.
PubMed: 38826462
DOI: 10.1101/2024.05.23.595594 -
Clinical Hematology International 2024Globally, multiple myeloma (MM) ranks 24 among the most common cancers. The Middle East and Africa are affected by an increasing trend in MM incidence, owing to several...
BACKGROUND
Globally, multiple myeloma (MM) ranks 24 among the most common cancers. The Middle East and Africa are affected by an increasing trend in MM incidence, owing to several underlying factors. This systematic review aims to assess the epidemiology, patient characteristics, and treatment outcomes associated with MM in selected countries in the Middle East and Africa.
METHODS
An electronic search was performed in the PubMed/MEDLINE database. Abstracts presented at the annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology and the GLOBOCAN registry were searched. Qualitative analysis was performed.
RESULTS
A total of 412 articles were screened, and 14 were selected. The five-year prevalence per 100,000 gathered from country-wise GLOBOCAN data ranged between 155 in Kuwait and 5,625 in North Africa. The identified treatment options were proteasome inhibitors such as bortezomib, drugs such as thalidomide, lenalidomide, dexamethasone, melphalan, and cyclophosphamide, and newer drugs such as daratumumab.
CONCLUSION
Improved diagnostic capability has increased the incidence of MM in this region. However, advanced drugs and treatment regimens remain unaffordable in many countries of these regions. Therefore, understanding the trends of the disease and improving healthcare settings are imperative.
PubMed: 38817690
DOI: 10.46989/001c.92555 -
Clinical Case Reports Jun 2024We report an observation of a young patient presenting with severe type 1 cryoglobulinemic vasculitis revealing a monoclonal gammopathy of clinical significant....
KEY CLINICAL MESSAGE
We report an observation of a young patient presenting with severe type 1 cryoglobulinemic vasculitis revealing a monoclonal gammopathy of clinical significant. Treatment with Melphalan-Thalidomide Prednisone improved the symptoms. Early diagnosis would prevent serious tissue damage.
ABSTRACT
Monoclonal gammopathy encompass diverse clinical forms. Only the cancerous form, multiple myeloma (MM), is treated based on specific diagnostic criteria. A new clinical entity, monoclonal gammopathy of clinical significance (MGCS), warrants special attention due to its need for specific treatment. It involves patients with signs of potentially severe organ involvement that do not meet MM criteria. We present the case of a 34-year-old Malagasy woman with severe type I cryoglobulinemic vasculitis associated with noncancerous monoclonal gammopathy, showing a favorable outcome after treatment with Thalidomide. Symptoms included toe necrosis, a severe ulcer on the left calf evolving for 3 months, and stocking-like dysesthesias. Investigations revealed monoclonal gammopathy at 30.1 g/L, proteinuria at 1 g/24 h, medullary plasma cell at 6%, and circulating cryoglobulin of Ig kappa type. CRAB criteria (anemia, hypercalcemia, renal insufficiency, and osteolysis) were absent. Treatment with Thalidomide, combined with corticosteroids and local care for 4 months, resulted in ulcer healing, disappearance of dysesthesias, and persistent normalization of gammaglobulin. Our case underscores the importance of specific treatment for MGCS.
PubMed: 38813450
DOI: 10.1002/ccr3.8897 -
Transplantation Proceedings May 2024Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood,...
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood, rarely occurring in adults. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for FHL. However, optimal conditioning regimens for adult-onset FHL have not yet been established. Herein, we report a case of adult-onset FHL. A 37-year-old man presented with fever, liver dysfunction, and pancytopenia, which improved temporarily with corticosteroid therapy. However, he later developed encephalitis and myelitis. Genetic analysis revealed rare variants of UNC13D (c.2367+1 g>a and c.2588 g>a), which were compound heterozygous pathogenic mutations. FHL type 3 was diagnosed, and treatment based on the hemophagocytic lymphohistiocytosis (HLH) 1994 protocol was initiated. The patient underwent cord blood transplantation (CBT) with myeloablative conditioning using fludarabine, melphalan, and total-body irradiation (TBI), which resulted in graft rejection. The patient was successfully rescued by a second CBT following reduced-intensity conditioning with fludarabine, cyclophosphamide, and TBI. Although graft failure is an important complication especially in CBT, it could be managed by appropriate treatment, and that cord blood would be a promising alternative source with the advantages of rapidity and avoidance of related donors with a high risk of harboring the same genetic mutation.
PubMed: 38811303
DOI: 10.1016/j.transproceed.2024.05.011