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Leukemia & Lymphoma Jul 2011
Topics: Busulfan; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Myeloablative Agonists; Neoplasms, Second Primary; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome
PubMed: 21612379
DOI: 10.3109/10428194.2011.572324 -
Pediatric Blood & Cancer Sep 2016The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using...
High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702).
BACKGROUND
The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS).
PROCEDURE
The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR.
RESULTS
The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%.
CONCLUSIONS
The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.
Topics: Adolescent; Central Nervous System Neoplasms; Chemoradiotherapy; Child; Child, Preschool; Craniospinal Irradiation; Female; Hepatic Veno-Occlusive Disease; Humans; Incidence; Induction Chemotherapy; Male; Neoplasms, Germ Cell and Embryonal
PubMed: 27203542
DOI: 10.1002/pbc.26074 -
Pediatric Blood & Cancer Jan 2023Stage 4a metastatic retinoblastoma (RB) is curable with intensive multimodality therapy including myeloablative chemotherapy with autologous stem cell transplant...
BACKGROUND
Stage 4a metastatic retinoblastoma (RB) is curable with intensive multimodality therapy including myeloablative chemotherapy with autologous stem cell transplant (HDC-ASCT) and involved field radiation therapy (IFRT). To our knowledge, no data exist on the impact of (a) pre-ASCT disease status, and (b) IFRT to sites of metastatic disease post ASCT on survival.
PROCEDURE
We retrospectively reviewed patients with stage 4a metastatic RB who underwent induction chemotherapy followed by HDC-ASCT, with or without IFRT, to residual tumor sites at Memorial Sloan Kettering Cancer Center (MSKCC) (n = 24).
RESULTS
The degree of postinduction response prior to ASCT did not affect outcome, with 5-year overall survival (OS) of 68% and 86% in patients who achieved complete response (CR) and very good partial response (VGPR)/partial response (PR) prior to ASCT, respectively. IFRT administered post ASCT in patients with possible residual bony metastatic disease increases the likelihood of developing osteosarcoma in the radiation field.
CONCLUSION
OS for patients with stage 4a metastatic RB treated with ASCT with VGPR or PR to pretransplant chemotherapy was not significantly different from patients with CR. In addition, IFRT does not seem to be required for bony disease control and increased the likelihood of developing osteosarcoma.
Topics: Humans; Disease-Free Survival; Retrospective Studies; Retinoblastoma; Antineoplastic Combined Chemotherapy Protocols; Transplantation, Autologous; Hematopoietic Stem Cell Transplantation; Retinal Neoplasms; Osteosarcoma; Treatment Outcome
PubMed: 35934994
DOI: 10.1002/pbc.29921 -
Biology of Blood and Marrow... Aug 2007To evaluate the potential of allogeneic hematopoietic cell transplantation (HCT) with a reduced-intensity conditioning regimen (RIST) for the treatment of patients with...
Comparable antileukemia/lymphoma effects in nonremission patients undergoing allogeneic hematopoietic cell transplantation with a conventional cytoreductive or reduced-intensity regimen.
To evaluate the potential of allogeneic hematopoietic cell transplantation (HCT) with a reduced-intensity conditioning regimen (RIST) for the treatment of patients with hematologic malignancies not in remission, we retrospectively reviewed the medical records of 132 patients (89 leukemia or myelodysplastic syndrome, 40 malignant lymphoma, and 3 others) who received conventional myeloablative HCT (CST, n=52) or RIST (n=80). The median age of the RIST group was significantly higher than that of the CST group (53 years versus 40 years, P<.01). The RIST group also included a higher proportion of patients with an HCT-specific comorbidity index (HCT-CI) of 1 or more than the CST group (65% versus 37%, P=.03). The probabilities of achieving complete remission and the incidences of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) in the CST and RIST groups were, respectively, 77% and 64%, 50% and 50%, and 23% and 28%, with no significant differences. Similarly, there was no difference in the 2-year probabilities of nonrelapse mortality (NRM, 36% and 38%), progressive disease or relapse (PD 51% and 49%), overall survival (OS, 31% and 38%), and progression-free survival (PFS, 28% and 29%). Multivariate analyses revealed that a higher HCT-CI score and transplant from donors other than HLA-matched relatives were associated with increased risks of NRM and poor OS, and patients who received chemotherapy within 2 months before HCT were associated with increased risks of PD, poor OS, and PFS after transplantation. After adjusting for these variables, the risks of NRM, PD, OS, and PFS in the RIST group were not significantly different from those in the CST group. In conclusion, these results suggest that the antileukemia/lymphoma effect associated with RIST is comparable to that associated with CST. RIST appears to be feasible for the treatment of hematologic malignancies not in remission.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Japan; Leukemia; Lymphoma; Male; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous
PubMed: 17640597
DOI: 10.1016/j.bbmt.2007.04.004 -
British Journal of Haematology Jan 2002Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these...
A sequence of immuno-chemotherapy with Rituximab, mobilization of in vivo purged stem cells, high-dose chemotherapy and autotransplant is an effective and non-toxic treatment for advanced follicular and mantle cell lymphoma.
Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these approaches, however, is not defined. We treated 10 patients with relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence of four phases, each designed to play a specific role in tumour eradication. After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide, vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none achieved a molecular response. After the immuno-chemotherapy phase, which combined Rituximab with vincristine and cyclophosphamide, seven patients were in complete response (CR) and three in good partial response (PR), and all those with a molecular marker of disease showed a disappearance of the signal from marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was effective in mobilizing an adequate number of progenitor cells that were polymerase chain reaction negative in all informative cases. Phase 4 consisted of high-dose therapy with autologous support followed by two doses of Rituximab. Autograft was performed in nine patients. The haematopoietic recovery was as expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell mobilization with in vivo purging and autotransplant, organized in four blocks of treatment, was simple to administer and devoid of toxic effects. It permits rapid attainment of clinical and molecular response and enables the harvest of lymphoma-free peripheral blood progenitor cells even in heavily pretreated patients with relapsed or refractory disease.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Purging; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Gene Rearrangement; Genes, bcl-2; Half-Life; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Male; Metabolic Clearance Rate; Middle Aged; Polymerase Chain Reaction; Prednisone; Recurrence; Rituximab; Transplantation, Autologous; Vincristine
PubMed: 11841421
DOI: 10.1046/j.1365-2141.2002.03256.x -
Biology of Blood and Marrow... 2000Central nervous system (CNS) involvement by non-Hodgkin's lymphoma (NHL) carries a poor patient prognosis whether it occurs as a primary site of disease or secondarily...
Central nervous system (CNS) involvement by non-Hodgkin's lymphoma (NHL) carries a poor patient prognosis whether it occurs as a primary site of disease or secondarily in patients with systemic disease. In a group of 481 patients undergoing high-dose therapy with hematopoietic cell transplantation (HCT) for NHL, 15 patients (3.1%) were identified with CNS involvement. Two patients had primary CNS lymphoma, and 13 had secondary disease. All patients received intrathecal chemotherapy, and 13 received CNS radiotherapy before transplantation. Fourteen patients received systemic chemotherapy. At the time of transplantation, both patients with primary CNS lymphoma and 8 patients with secondary disease had achieved a complete response, 3 patients had achieved a partial response, 1 had failed induction therapy, and 1 had progression of CNS disease before high-dose therapy. Fourteen patients received carmustine, etoposide, and cyclophosphamide as the preparative regimen, and 1 patient received fractionated total body irradiation instead of carmustine. The 2 patients with primary CNS lymphoma were alive and free of disease, 1 at 1,085 days after HCT and 1 at 3,704 days after HCT. The actuarial 5-year event-free survival (EFS) was 46% +/- 26%, and overall survival (OS) was 41% +/- 28%. The median EFS and OS were 2.2 and 1.5 years, respectively. Three patients experienced symptomatic memory loss or intellectual decline after therapy, 1 patient developed paraplegia, and 1 patient had a thrombotic stroke 20 months after HCT. Despite treatment-related toxicities, 7 patients responding to quality-of-life questions at approximately 1 year after HCT gave their overall quality of life a median rating of 9 out of a possible 10 (range, 6-10). High-dose therapy with autologous HCT can produce extended EFS in patients with secondary CNS lymphoma and possibly in those with primary CNS NHL.
Topics: Actuarial Analysis; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Carmustine; Central Nervous System; Central Nervous System Neoplasms; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Disease Progression; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Myelitis, Transverse; Neoplasm Invasiveness; Quality of Life; Radiation Injuries; Survival Analysis; Survival Rate; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation
PubMed: 10905773
DOI: 10.1016/s1083-8791(00)70060-7 -
Experimental and Clinical... Dec 2018We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia... (Comparative Study)
Comparative Study
OBJECTIVES
We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant.
MATERAILS AND METHODS
Twenty patients with primary acute myeloid leukemia had been randomized into busulfan/fludarabine and modified busulfan/cyclophosphamide groups. We retrospectively compared hematopoietic engraftment, regimen-related toxicity, graft-versus-host disease, transplant-related mortality, leukemia-free survival, and overall survival between the groups.
RESULTS
All patients achieved engraftment with 100% donor chimerism. The median times for the neutrophil and platelet engraftment in the busulfan/fludarabine and modified busulfan/cyclophosphamide groups were 14.1 versus 14.3 days and 12.7 versus 12.2 days, respectively. Significantly lower incidences of pretreatment toxicity, blood transfusion, and virus activation were observed in the busulfan/fludarabine group. Acute grade 1 graft-versus-host-disease developed in all patients, which was successfully controlled with methylprednisolone. There were no significant differences in engraftment, graft-versus-host disease, leukemia-free survival, and overall survival between groups. Both of these conditioning regimens achieved stable engraftment. Regimen-related toxicity in the busulfan/fludarabine group was well tolerated compared with that in the modified busulfan/cyclophosphamide group, without an increase in relapse rate.
CONCLUSIONS
Our results demonstrated that myeloablative busulfan/fludarabine might be a highly effective and low-toxicity alternative for patients with acute myeloid leukemia.
Topics: Adolescent; Adult; Busulfan; China; Cyclophosphamide; Disease-Free Survival; Drug Therapy, Combination; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Middle Aged; Myeloablative Agonists; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Time Factors; Transplantation Conditioning; Transplantation, Haploidentical; Treatment Outcome; Vidarabine; Young Adult
PubMed: 29790457
DOI: 10.6002/ect.2017.0100 -
PloS One 2014The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin,... (Randomized Controlled Trial)
Randomized Controlled Trial
The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical trials registration unique identifier: NCT00001137.
Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; Cohort Studies; DNA, Viral; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Lymphoma, AIDS-Related; Male; Middle Aged; Viremia
PubMed: 24638072
DOI: 10.1371/journal.pone.0092118 -
Blood Dec 1994The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated...
The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated within 1 year of initial therapy. Forty-five patients were consolidated during remission, and 27 patients were treated for primary refractory disease. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients who had responded previously, myeloablative therapy increased the rate of complete remission from 5% to 45% (P < .01) but did not prolong progression-free intervals or survival times. The same treatment controlled the myeloma in 70% of patients with primary resistant disease and prolonged the median survival from 37 to 83 months (P = .03). Intensive treatment for primary resistant myeloma administered later in the disease course resulted in significantly lower response rates and shorter progression-free intervals. Current myeloablative regimens supported by autologous stem cells appeared useful primarily in patients with primary resistant disease during the first year of therapy.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Resistance; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Life Tables; Melphalan; Middle Aged; Multiple Myeloma; Radiation Injuries; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Analysis; Thiotepa; Treatment Outcome; Vincristine; Whole-Body Irradiation
PubMed: 7994043
DOI: No ID Found -
A systematic review of re-induction chemotherapy for children with relapsed high-risk neuroblastoma.European Journal of Cancer (Oxford,... Apr 2019Despite aggressive multimodal therapy, >50% of children with high-risk neuroblastoma (HRNB) relapse. Survival after relapse is rare, and no consensus currently exists on...
BACKGROUND
Despite aggressive multimodal therapy, >50% of children with high-risk neuroblastoma (HRNB) relapse. Survival after relapse is rare, and no consensus currently exists on the most effective therapy.
OBJECTIVE
To conduct a systematic review of the literature on effectiveness of re-induction chemotherapy in children with relapsed HRNB.
METHODS
Database searches were performed to identify studies looking at response to 1st line chemotherapy for children >12 months at diagnosis with first relapse of HRNB. Studies not reporting separate outcomes for HRNB patients or of refractory patients only were excluded. Two independent reviewers extracted the data and assessed study quality using a modified Newcastle-Ottawa tool.
RESULTS
Nine studies were identified fitting the inclusion criteria. All except one were single arm cohorts, and two were retrospective database reviews from single centres. One was a multicentre randomised controlled trial. All used a version of the validated International Neuroblastoma Response Criteria with 8 recording best ever response and 1 at a specified time, and 5 had central review. The proportion of relapsed patients varied from 24 to 100% with 30-93% receiving upfront myeloablative therapy. The response rate varied from 6 to 64%; however, because of heterogeneity, studies were not directly comparable, and no single treatment emerged as the most effective re-induction therapy.
CONCLUSIONS
To date, there is no clear superior re-induction therapy for 1st relapse of HRNB. Randomised controlled trials with separate arms for relapsed versus refractory disease are needed to determine optimal re-induction chemotherapy to act as a backbone for testing newer targeted agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Humans; Induction Chemotherapy; Infant; Male; Neoplasm Recurrence, Local; Neuroblastoma
PubMed: 30822684
DOI: 10.1016/j.ejca.2018.12.032