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2.
Eur J Haematol ; 112(3): 392-401, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37933194

ABSTRACT

OBJECTIVE: There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of pegaspargase-containing ALL regimens (PEG-CAR) in young adults however, outcomes in Hispanic ethnicity continue to be underreported. METHODS: We evaluated outcomes of newly diagnosed, adult B-cell ALL Hispanic and non-Hispanic patients consecutively treated with a PEG-CAR or HyperCVAD between January 2011 and November 2022. The primary endpoint was event-free survival (EFS) while secondary endpoints included cumulative incidence of relapse and overall survival (OS). RESULTS: Among 105 included patients, 48 (45.7%) were treated with a PEG-CAR and 57 (54.3%) with HyperCVAD. Median age was 38 years (range, 18-75 years), 61% were Hispanic, and 35.2% had poor-genetic risk. Hispanic patients demonstrated significantly worse 5-year EFS with a PEG-CAR compared to that seen with HyperCVAD (HR, 2.58; 95% CI, 1.32-5.04; p = .006) whereas non-Hispanic patients had better outcomes with PIR (52.4% vs. 42.0%). Hispanic ethnicity (p = .015) and male sex (p = .019) were independent predictors for poor OS. CONCLUSIONS: Hispanic patients with B-cell ALL had worse EFS with a PEG-CAR as compared with HyperCVAD. Future studies will aim to confirm these findings and establish a tailored treatment approach for this high-risk population.


Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Young Adult , Humans , Male , Adult , Asparaginase/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Polyethylene Glycols/adverse effects , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Retrospective Studies
3.
Int J Surg Pathol ; : 10668969231211338, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37960848

ABSTRACT

Emanating from a discrete category within the lympho-hematopoietic tumor system, as established by the World Health Organization in 2008, the blastic plasmacytoid dendritic cell neoplasm constitutes an uncommon malignant hematological disorder. It is routinely misidentified on account of its conspicuous dermatological manifestation, yet may insidiously permeate bone marrow and lymph nodes, involving peripheral blood and diverse extra-nodal tissues. Instances of mammary gland encroachment are extraordinarily infrequent. The current document delineates a case of a 14-year-old female patient contending with blastic plasmacytoid dendritic cell neoplasm, whose primary symptom was a mammary nodule, and whose breast and bone marrow/blood involvement were synchronous, in attempt to increase clinical vigilance.

4.
Eur J Haematol ; 111(6): 863-871, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37670560

ABSTRACT

OBJECTIVES: We recently performed a single-arm phase II trial of DA-EPOCH in adults with acute lymphoblastic leukemia (ALL). We sought to compare these results to those with standard Hyper-CVAD. METHODS: We created a retrospective matched cohort of patients who received Hyper-CVAD (n = 69) at our center and otherwise met eligibility criteria for the DA-EPOCH trial (n = 53). RESULTS: Our outcomes support the use of Hyper-CVAD over DA-EPOCH in Ph- disease for both overall survival (OS; HR 0.18, p = .004) and event-free survival (EFS; HR 0.51, p = .06). In contrast, outcomes were similar in Ph+ disease (OS HR 0.97, p = .96; EFS HR 0.65, p = .21). Rates of morphologic remission and measurable residual-disease negativity were similar between the regimens. Hyper-CVAD was associated with significantly more febrile neutropenia (OR 1.9, p = .03) and a greater incidence of Grade 4 or 5 adverse events (20% vs. 6%). Average transfusions per cycle of both red blood cells (p < .001) and platelets (p < .001) were five-fold higher with Hyper-CVAD. CONCLUSIONS: Our findings support continued use of Hyper-CVAD for Ph- ALL but suggest that DA-EPOCH may be a reasonable alternative for Ph+ ALL. These data also highlight a potential role for DA-EPOCH in resource-limited settings or when more intense therapy is not feasible.


Subject(s)
Doxorubicin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Retrospective Studies , Doxorubicin/therapeutic use , Cyclophosphamide/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Vincristine/therapeutic use , Dexamethasone
5.
Leuk Res ; 130: 107316, 2023 07.
Article in English | MEDLINE | ID: mdl-37245332

ABSTRACT

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adolescent , Young Adult , Child , Retrospective Studies , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Doxorubicin/therapeutic use , Cyclophosphamide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dexamethasone/adverse effects , Vincristine/therapeutic use , Multicenter Studies as Topic
6.
Eur J Haematol ; 111(1): 154-160, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37086155

ABSTRACT

Treatment of acute lymphoblastic leukemia (ALL) requires both systemically and locally directed therapies to prevent central nervous system (CNS) recurrence. In response to restrictions brought on by the COVID-19 pandemic, our institution adopted triple intrathecal (IT) chemotherapy for CNS prophylaxis during HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). We retrospectively reviewed records of newly diagnosed adult all patients who were consecutively treated with HyperCVAD between January 2011 and July 2022. Outcomes of patients who received triple IT chemotherapy and standard of care (SOC) CNS prophylaxis were compared. The primary endpoint was CNS relapse-free survival (RFS) while secondary endpoints included cumulative incidence of relapse, overall survival, number of outpatient, and total ITs per patient, and CNS treatment-related toxicities. A total of 37 patients including 21 in the triple IT and 16 in the SOC cohorts were evaluated. There were no differences between the triple IT and SOC cohorts with respect to CNS-RFS (89.6% vs. 80.4%; HR, 1.55; 95% CI, 0.45-5.39; p = .49), cumulative incidence of relapse (8.9% vs. 19.6%; HR, 1.14; 95% CI, 0.3-5.3; p = .87), and overall survival (89.6% vs. 85.7%; HR, 0.91; 95% CI, 0.20-4.21; p = .90) at 2-years. Significantly fewer IT doses were administered in the triple IT cohort (p = .011) and the number of additional outpatient appointments to administer IT chemotherapy were markedly reduced as 98.6% of IT doses were administered during scheduled admissions compared to 76.8% (p < .001). The adoption of triple IT chemotherapy did not increase CNS treatment-related toxicities but rather, the inverse was observed. Triple IT chemotherapy during HyperCVAD represents a feasible alternative to SOC CNS prophylaxis, especially during times of resource restriction and when minimization of patient exposures is desired.


Subject(s)
COVID-19 , Central Nervous System Neoplasms , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adult , Retrospective Studies , Pandemics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Cyclophosphamide/therapeutic use , Methotrexate/therapeutic use , Recurrence , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/prevention & control , Vincristine/adverse effects
7.
Clin Lymphoma Myeloma Leuk ; 23(4): 238-243, 2023 04.
Article in English | MEDLINE | ID: mdl-36872149

ABSTRACT

Combination chemotherapy is the mainstay of treatment for acute lymphoblastic leukemia (ALL). The Hyper-CVAD regimen was developed in 1992 at MD Anderson Cancer Center and has since become a standard of care option for adult patients with ALL. Since its conception, a number of modifications have been implemented to customize the regimen for different patient populations and safely incorporate novel therapies without compromising tolerability. We aim to review the evolution of the Hyper-CVAD regimen over the past 3 decades, focusing on clinical pearls, as well as future directions.


Subject(s)
Doxorubicin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Doxorubicin/therapeutic use , Cyclophosphamide/therapeutic use , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Dexamethasone/therapeutic use , Vincristine/therapeutic use
8.
Proc (Bayl Univ Med Cent) ; 36(2): 240-242, 2023.
Article in English | MEDLINE | ID: mdl-36876257

ABSTRACT

Burkitt-like lymphoma with 11q aberration is a rare condition that poses a diagnostic challenge due to similarities with Burkitt's lymphoma. Due to the rarity of cases, no specific guidelines exist for therapy, and it is treated the same way as Burkitt's lymphoma. We present such a case with initial orbital involvement, an unusual manifestation. Our patient achieved remission with induction chemotherapy, although he will need regular follow-up given the paucity of information on long-term monitoring in these patients.

9.
Eur J Haematol ; 110(2): 168-176, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36321745

ABSTRACT

Multi-parametric flow cytometry (MFC) has a well-established role in measurable residual disease (MRD) monitoring in patients with B-lymphoblastic leukemia (B-ALL). However, the optimal time-point (TP) for early MRD testing and associated prognostic impact remain undefined in adult B-ALL patients receiving Hyper-CVAD induction chemotherapy. To evaluate the utility of MRD analysis after one cycle (TP1) in comparison to MRD analysis after two cycles (TP2) of induction treatment with Hyper-CVAD chemotherapy, we studied 49 adult B-ALL patients over a 10-year period (2010-2020) who had available bone marrow samples for morphological and MFC MRD assessments at the two separate TPs. Median times to TP1 and TP2 relative to start of treatment were 21 and 45 days, respectively. When censored at transplant, achievement of MRD negativity at TP1 was not associated with a statistically significant improvement in either event-free survival (EFS) (p = .426) or overall survival (OS) (p = .335) when compared to patients with MRD positivity. In contrast, achieving MRD negativity at TP2 was associated with a statistically significant improvement in both EFS (p = ·005) and OS (p = .047) over patients who remained MRD positive. Multivariate analysis demonstrated that KMT2A-rearrangement and MRD positivity at TP2 were the only significant predictors of outcome, correlating with worse EFS and OS. Therefore, in the absence of residual morphologic disease, MRD analysis after one cycle of Hyper-CVAD induction chemotherapy did not provide additional benefit with regard to risk stratification or correlation with survival outcomes when compared to MRD testing after two cycles of Hyper-CVAD in adult B-ALL patients.


Subject(s)
Induction Chemotherapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adult , Flow Cytometry , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Neoplasm, Residual/diagnosis
10.
Stem Cells Transl Med ; 11(11): 1113-1122, 2022 11 18.
Article in English | MEDLINE | ID: mdl-36181762

ABSTRACT

Post-remission strategies for patients with acute lymphoblastic leukemia (ALL) are limited to the multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT), and cellular therapies are seldom involved. Although chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) has been studied in patients with acute myeloid leukemia, its efficacy in ALL is still undetermined. We enrolled 48 patients receiving hyper-CVAD-based MST between July 1, 2009, and January 31, 2018. No acute or chronic graft-versus-host disease occurred in patients receiving MST. Four-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, and the 4-year relapse rate was 65%. No patient experienced non-relapse mortality. Subgroup analysis showed that OS rates were comparable between groups with different age, risk stratification, minimal residual disease status prior to MST and immunophenotype. Adult patients tended to achieve better 4-year LFS (62% vs. 26%, P = .058) and lower hematologic relapse rate (38% vs. 74%, P = .058) compared with adolescent and young adult patients. Donor chimerism/microchimerism was detectable ranging from 0.002% to 42.78% in 78% (42/54) available samples within 14 days after each infusion and at 3 months or one year after the last cell infusion. Multivariate analyses demonstrated that white blood cells <30 × 109/L at diagnosis and sufficient hyper-CVAD cycles were prognostic factors for better 4-year OS and LFS, while the B-cell phenotype and higher number of infused CD34+ cells in the first cycle were predictors for favorable 4-year LFS. The hyper-CVAD-based MST was a feasible strategy for treating ALL patients with mild toxicity.


Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Leukocytes, Mononuclear , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Retrospective Studies
11.
Leuk Res ; 119: 106885, 2022 08.
Article in English | MEDLINE | ID: mdl-35738024

ABSTRACT

BACKGROUND: Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. We sought to validate those findings in previously untreated adult patients with Ph+ ALL. METHODS: This was a retrospective study analyzing the outcomes of previously untreated adult ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated with ponatinib plus hyper-CVAD. RESULTS: 82 patients were included. The median age was 51 years. The median follow-up was 2.62 years. The 5-year overall survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk cytogenetics to be associated with inferior outcomes, while CD20 + predicted favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was associated with better OS and EFS on univariate and multivariate analysis. CONCLUSION: Our data supports the use of ponatinib plus hyper-CVAD as a standard of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show that advances are still needed in the frontline setting, and clinical trial enrollment is recommended.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Doxorubicin/therapeutic use , Humans , Imidazoles , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyridazines , Retrospective Studies , Vincristine/therapeutic use
12.
Arch Med Sci ; 18(1): 121-128, 2022.
Article in English | MEDLINE | ID: mdl-35251415

ABSTRACT

INTRODUCTION: Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) has become a popular regimen for adults with acute lymphoblastic leukemia (ALL). We assessed the efficacy and tolerability of hyper-CVAD in the treatment of adult ALL. MATERIAL AND METHODS: We retrospectively reviewed ALL patients aged 18 or above receiving the hyper-CVAD regimen. We assessed complete remission rate and overall survival, as well as hepatitis B carrier rate and hepatitis flare due to hepatitis B virus (HBV) reactivation. RESULTS: Fifty-two patients were treated with the hyper-CVAD regimen. The median age at diagnosis was 42 years; 27% of patients were Philadelphia (Ph) chromosome positive. The complete remission (CR) rate was 90.4% after the first cycle of chemotherapy. The induction mortality rate was 1.9%. Three patients required two cycles of hyper-CVAD to achieve CR. The median overall survival was 39.6 months and the 5-year overall survival was 50%. Age over 30 years and white blood cell count of more than 30 × 109/l were found to be prognostic for poor overall survival in multivariate analysis. The hepatitis B carrier rate was 17% in our cohort, and the rate of hepatitis flare due to HBV reactivation was 11% in patients with current infection. CONCLUSIONS: Hyper-CVAD is feasible and tolerable with a good CR rate in the treatment of adult ALL patients. It is an option for the treatment of ALL. Antiviral prophylaxis should be considered in ALL patients with HBV infection to reduce the risk of HBV reactivation.

13.
Cancer ; 127(15): 2641-2647, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33823073

ABSTRACT

BACKGROUND: Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has dramatically improved with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with tyrosine kinase inhibitors (TKIs). METHODS: The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib. RESULTS: In the CML-LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML-LBP. The BCR-ABL1 transcript was p210 in 22 patients (96%) and p190 in 1 patient (4%). In the Ph-positive ALL cohort, p210 and p190 transcripts were detected in 13 patients (21%) and 48 patients (77%), respectively. Patients with CML-LBP were less likely to achieve deep molecular remission than patients with Ph-positive ALL: the major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). Survival outcomes were similar for CML-LBP and Ph-positive ALL: the 5-year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML-LBP (5-year OS rate, 88% vs 57%; P = .04). In Ph-positive ALL, the outcome was driven by deeper molecular remission: the 5-year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). CONCLUSIONS: The outcome of CML-LBP has improved with hyper-CVAD plus dasatinib therapy with survival comparable to that of Ph-positive ALL. Further improvement may be achieved with the use of novel TKIs and targeted agents.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dasatinib/therapeutic use , Dexamethasone , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
14.
EJHaem ; 2(4): 774-784, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35845206

ABSTRACT

Patients with high-risk aggressive B-cell lymphoma exhibit poor survival after R-CHOP. More intensive regimens yield higher rates of remission but also of complication. We investigated all 401 patients < 70 years with high-risk (age-adjusted [aa] international prognostic index [IPI] ≥2, extranodal, or bulky) aggressive B-cell lymphoma hospitalized at Karolinska for urgent start of immunochemotherapy (129 R-Hyper-CVAD; 261 R-CHOP/R-CHOEP). Patients showed IPI 3-5 (70%), WHO PS ≥2 (49%), bulky disease (70%), extranodal (75%) and CNS (8%) involvement. Five-year overall/progression-free survival (OS/PFS) was better in patients who started R-Hyper-CVAD (84%/77%) compared with R-CHOP/R-CHOEP (66%/55%). Differences were independent in multivariable analysis, seen in all patient categories, and accentuated in extreme high-risk disease: R-Hyper-CVAD vs. R-CHOP/R-CHOEP showed 5-year PFS 69% vs.40% in aaIPI 3 and 88% vs. 38% in CNS involvement. For validation, survival was compared between the two Karolinska sites and calendar periods. Survival was superior 2006-2010 at the site that introduced R-Hyper-CVAD/R-MA 2006, identical at both sites 2011-2017 after the other site adopted R-Hyper-CVAD/R-MA 2011, and excellent 2018-2020 when R-Hyper-CVAD/R-MA use increased to 75% of patients. Despite considerable toxicity, also patients aged 61-69 years showed better survival with R-Hyper-CVAD/R-MA. This is the largest single-centre series of patients treated with R-Hyper-CVAD/R-MA, showing favourable outcome in high-risk aggressive B-cell lymphoma.

15.
Hematology ; 26(1): 26-30, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33357100

ABSTRACT

Objectives: Low pretreatment platelet count is negatively associated with overall survival (OS) of certain subtypes of acute lymphoblastic leukemia (ALL). However, the prognostic impact of the grade of thrombocytopenia on OS and disease-free survival (DFS) has never been explored. Methods: We conducted an extended analysis of a retrospective study. Newly diagnosed adults with ALL was enrolled in this study. The grade of thrombocytopenia was evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Prognostic impacts were assessed by the hazard ratios (HRs) and 95% confidence intervals (CIs) obtained from univariate and multivariate Cox proportional hazards regression analyses. Results: A total of 90 participants were included in this study. There were 18 cases with grade 4 thrombocytopenia among the 71 participants presented with thrombocytopenia of any grade. Both univariate and multivariate Cox regression analyses suggested the independent negative prognostic impact of grade 4 thrombocytopenia on both OS (HR = 4.73, 95% CI = 1.95-11.52) and DFS (HR = 9.82, 95% CI = 3.14-30.76) of adult ALL, using the cohort of patients with no thrombocytopenia as a reference. In addition, treatment regimen, cytogenetic profile, time to treatment, and platelet count were independent prognostic factors of the OS. We also found that treatment regimen, cytogenetic profile, and peripheral blood blast percentage were independent prognostic factors of the DFS. Conclusion: Grade 4 thrombocytopenia was a negative prognostic factor for both overall survival and disease-free survival of adults with acute lymphoblastic leukemia.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Thrombocytopenia/complications , Adolescent , Adult , Female , Humans , Male , Middle Aged , Platelet Count , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Thrombocytopenia/diagnosis , Young Adult
16.
Hematol Oncol Stem Cell Ther ; 14(1): 71-75, 2021 Mar.
Article in English | MEDLINE | ID: mdl-30291826

ABSTRACT

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a rare disease characterized by aggressive clinical course and short survival. All available data are extracted from case reports and case series. The outcome is dismal and only two reported cases were cured after several lines of therapies including stem cell transplant. We herein present the case of a patient with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic symptoms. He was treated with aggressive multiagent chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in durable complete remission with no evidence of disease recurrence after 58 months of follow-up. This is the first reported case of durable remission after first-line treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , CD8-Positive T-Lymphocytes , Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell , Skin Neoplasms , Adult , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Humans , Lymphoma, T-Cell/metabolism , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/therapy , Male , Methotrexate/administration & dosage , Remission Induction , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Vincristine/administration & dosage
17.
Ann Hematol ; 99(9): 2119-2124, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32676733

ABSTRACT

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Biphenotypic, Acute/diagnosis , Leukemia, Biphenotypic, Acute/drug therapy , Adult , Aged , Cohort Studies , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Doxorubicin/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Vincristine/therapeutic use , Young Adult
18.
Curr Oncol Rep ; 22(4): 33, 2020 03 06.
Article in English | MEDLINE | ID: mdl-32144513

ABSTRACT

PURPOSE OF REVIEW: Burkitt's lymphoma and its leukemic form (Burkitt cell acute lymphoblastic leukemia) are a highly aggressive disease. We review the classification, clinical presentation, histology, cytogenetics, and the treatment of the disease. RECENT FINDINGS: Burkitt's lymphoma might be associated with tumor lysis syndrome which is a potentially fatal complication that occurs spontaneously or upon initiation of chemotherapy. Major improvements were made in the treatment of pediatric and adults population using short-course dose-intensive chemotherapy regimens, usually 1 week after a prephase induction. Addition of Rituximab to chemotherapy has become a standard of care. Relapsed/refractory disease has a very poor prognosis and the benefit from autologous/allogeneic hematopoietic stem cell transplant remains uncertain. Rituximab-based short-course dose-intensive chemotherapy is the standard of care of Burkitt's lymphoma even in the immunodeficiency-related form.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Burkitt Lymphoma/therapy , Hematopoietic Stem Cell Transplantation/methods , Rituximab/administration & dosage , Antigens, CD20/metabolism , Burkitt Lymphoma/genetics , Burkitt Lymphoma/metabolism , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 8/genetics , Humans , Proto-Oncogene Proteins c-bcl-6/metabolism , Translocation, Genetic
19.
Cancer ; 126(6): 1152-1160, 2020 03 15.
Article in English | MEDLINE | ID: mdl-31794095

Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/administration & dosage , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Age Factors , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brain Neoplasms/prevention & control , Brain Neoplasms/secondary , Constipation/chemically induced , Constipation/prevention & control , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytarabine/adverse effects , Cytarabine/metabolism , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Monitoring/methods , Fusion Proteins, bcr-abl/antagonists & inhibitors , Genetic Predisposition to Disease , Humans , Injections, Spinal , Intercellular Signaling Peptides and Proteins/therapeutic use , Kidney/drug effects , Methotrexate/adverse effects , Methotrexate/metabolism , Ophthalmic Solutions/administration & dosage , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prednisone/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Vincristine/administration & dosage , Vincristine/adverse effects
20.
Leuk Lymphoma ; 60(14): 3417-3425, 2019 12.
Article in English | MEDLINE | ID: mdl-31304820

ABSTRACT

We present an analysis of 98 consecutive patients with peripheral T-cell lymphoma (PTCL) treated over a 10-year period within Western Australia. The most common frontline therapies were CHO(E)P (47%), HyperCVAD (21%), and reduced intensity therapy or supportive care alone (19%). Median and 4-year overall survival (OS) for the whole cohort were 1.59 years and 34%. Amongst CHO(E)P and HyperCVAD-treated patients, elevated LDH, advanced stage, IPI >1, and non-ALK + ALCL histology predicted inferior progression-free survival (PFS). Inferior OS was predicted by elevated LDH, age >60, IPI >1, and non-ALK + ALCL histology. Response rates and PFS were not significantly different between patients treated with CHO(E)P or HyperCVAD. OS was longer in the HyperCVAD group, however this was not significant on multivariable analysis and appears to relate to the younger age and more aggressive therapy at relapse in this group. Our data confirmed the prognostic utility of the IPI in patients with PTCL and do not demonstrate a clear benefit of HyperCVAD.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large-Cell, Anaplastic/mortality , Lymphoma, T-Cell, Peripheral/mortality , Neoplasm Recurrence, Local/mortality , Stem Cell Transplantation/methods , Adolescent , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphoma, Large-Cell, Anaplastic/pathology , Lymphoma, Large-Cell, Anaplastic/therapy , Lymphoma, T-Cell, Peripheral/pathology , Lymphoma, T-Cell, Peripheral/therapy , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Retrospective Studies , Survival Rate , Western Australia , Young Adult
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