We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors.
We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study.
A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%±16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%±18.7% of cases with CR vs. 0% of cases with non-CR, P=0.07).
Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment.
Ewing sarcoma; High-dose chemotherapy; Stem cell transplantation
Treatment outcome in elderly Acute Myeloid Leukemia (AML) is still very disappointing. Although complete remission rate is around 50–60% the 2 years survival is only in the magnitude of 10–20%. This is mainly due to an overrepresentation of adverse prognostic factors present in elderly AML. As relapses emerge from residual disease present after chemotherapy, intensification of treatment could emerge as a rational strategy. Intensification of chemotherapy by increasing the dose of anthracyclines or addition of gemtuzumab ozogamycin (Mylotarg) to standard chemotherapy indeed has proved to be of advantage in elderly AML. In younger AML autologous peripheral blood stem cell transplantation (AuPBSCT) as post remission treatment in comparison to intensive consolidation chemotherapy has been investigated in a few randomized studies. AuPBSCT showed reduced relapse rates with low non-relapse mortality rates. In elderly AML intensification by AuPBSCT also have been performed although randomized studies are lacking. Nevertheless, in the previous years various reports have suggested the potential utility of AuHSCT in AML of the elderly with encouraging results, albeit mostly in highly selected patients. Acceptable toxicity and a relatively low rate of transplant-related mortality has been notified. However relapses occurred which, irrespective of age, still remains the major cause of treatment failure of AuHSCT in AML. In this review we summarize the experience of AuPBSCT in elderly AML.
We describe two unrelated patients who exhibited multiple chromosomal abnormalities in donor cells after allogeneic peripheral blood stem cell transplantation (PBSCT). The patients were diagnosed with chronic myeloid leukemia and chronic lymphocytic leukemia, respectively, and both underwent non-myeloablative conditioning with cyclophosphamide and fludarabine followed by PBSCT from their HLA-matched opposite-sex siblings. Post-transplant bone marrow cytogenetics showed full engraftment, and the early post-transplant studies demonstrated only normal donor metaphases. Subsequent studies of both patients, however, revealed a population of metaphase cells with abnormal, but apparently balanced, karyotypes. Chromosome studies performed on peripheral blood cells collected from both donors after transplantation were normal. Both patients remained in clinical remission during follow-up of up almost 6 years, despite the persistence of the abnormal clones. Chromosomal abnormalities in residual recipient cells after bone marrow or PBSCT are not unusual. In contrast, only rare reports of chromosome abnormalities in donor cells exist, all of which have been associated with post-bone marrow transplant myelodysplastic syndrome or acute leukemias. Ours is the first report of persistent clonal non-pathogenic chromosome aberrations in cells of donor origin.
Allogenic peripheral blood stem cell transplantation (Allo-PBSCT) is being used to treat hematological malignancies with increasing frequency. Graft-versus-host disease (GvHD) is a complex complication of PBSCT. A 43-year-old woman came to the gynecology clinic for amenorrhea. She had been diagnosed with acute myeloid leukemia 2 years earlier and treated with induction and consolidation chemotherapy. After developing complete remission, she underwent Allo-PBSCT. When she started chemotherapy, her menstrual cycle completely disappeared. Fourteen months after menopausal hormone replacement therapy, it was discovered that her upper vaginal canal was completely obstructed. The lower vagina had an atrophic appearance. We report a rare case of partial vaginal obstruction as a complication of chronic GvHD and review the literature. We expect that this case report provides an opportunity to remind clinician of the gynecologic complications of GvHD.
Graft vs host disease; Hematocolpos; Peripheral blood stem cell transplantation; Vagina
Granulocytic sarcoma (GS) represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML). We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT). The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.
The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
Recurrence; Medulloblastoma; Transplantation, Autologous; Tandem; Hematopoietic Stem Cell Transplantation
Intracranial granulocytic sarcomas are rare tumors, which are composed of immature granulocytic cells. Although it has been well known that these tumors are associated with acute myeloblastic leukemia (AML), they have been almost always related to bone marrow relapse. However, isolated recurrence of granulocytic sarcoma following complete remission from prior AML is extremely rare, especially in the central nervous system. A 44-year-old male presented with isolated recurrence of granulocytic sarcoma mimicking a falx meningioma two years after complete remission by allogenic peripheral blood stem cell transfusion (PBSCT) in the acute myelomonoblastic leukemia (FAB, M4). Because of depressed mental state and mass effect, total surgical resection was performed. Pathological findings were compatible with the granulocytic sarcoma. There was no evidence of leukemic relapse in the peripheral blood. We suggest that this phenomenon can be explained by the hypothesis that a certain barrier effect such as blood brain barrier might lead to the proliferation of intracranial leukemic cells which metastasized before PBSCT.
Chloroma; Granulocytic sarcoma; Leukemia
This prospective study was designed to determine the safety and efficacy of cyclophosphamide, BCNU and etoposide (CBV) conditioning and autologous peripheral blood stem cell transplant (PBSCT) in children with relapsed or refractory Hodgkin and non-Hodgkin lymphoma (HL and NHL).
Patients and Methods
Patients achieving CR or PR after 2–4 courses of reinduction underwent a G-CSF mobilized PBSC apheresis with a target collection dose of 5×106 CD34+/kg. Those eligible to proceed received autologous PBSCT after CBV (7200 mg/m2, 450–300 mg/m2, 2400 mg/m2).
Forty-three of 69 patients (30/39 HL, 13/30 NHL) achieved a CR/PR after reinduction. Thirty-eight patients (28 HL, 10 NHL) underwent PBSCT. All initial 6 patients who received BCNU at 450 mg/m2 experienced grade III or IV pulmonary toxicity compared to none of the subsequent 32 receiving 300 mg/m2 (p<0.0001). The probability of OS at 3 years for all patients is 51% and for transplanted patients is 64%. The 3-year EFS is 38% (45% for HL; 30% NHL). The 3-year EFS in transplanted patients is 66% (65% HL; 70% NHL). Initial duration of remission of ≥ 12 vs < 12 months was associated with a significant increase in OS (3 ys OS 70% vs 34%) (p=0.003).
BCNU at 300 mg/m2 in a CBV regimen prior to PBSCT is well tolerated in relapsed or refractory pediatric lymphoma patients. A short duration (< 12 months) of initial remission is associated with a poorer prognosis. Lastly, a high percentage of patients achieving a CR/PR after reinduction therapy can be salvaged with CBV and autologlous PBSCT.
autologous transplant; PBSCT; CBV; lymphoma; NHL; HL
Double high-dose chemotherapy (HDCT) was applied to 18 patients with highrisk neuroblastoma including 14 patients who could not achieve complete response (CR) even after the first HDCT. In 12 patients, successive double HDCT was rescued with peripheral blood stem cells collected during a single round of leukaphereses and in 6 patients, second or more rounds of leukaphereses were necessary after the first HDCT to rescue the second HDCT. The median interval between the first and second HDCT (76 days; range, 47-112) in the single harvest group was shorter than that (274.5 days; range, 83-329) in the double harvest group (p<0.01). Hematologic recovery was slow in the second HDCT. Six (33.3%) treatment-related mortalities (TRM) occurred during the second HDCT but were not related to the shorter interval. Disease-free survival rates at 2 years with a median follow-up of 24 months (range, 6-46) in the single and double harvest group were 57.1% and 33.3%, respectively. These results suggest that successive double HDCT using the single harvest approach may improve the survival of high-risk patients, especially who could not achieve CR after the first HDCT despite delayed hematologic recovery and high rate of TRM during the second HDCT.
Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.
Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies.
Acute lymphoblastic leukemia; non-Hodgkin's lymphoma; osteosarcoma; secondary cancer
Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies.
Patients and Methods
To provide the totality of research evidence related to the effects of PBSCT versus BMT, we conducted an individual-patient data meta-analysis using data from nine randomized trials enrolling 1,111 adult patients.
Compared with BMT, PBSCT led to faster neutrophil (odds ratio [OR] = 0.31; 95% CI, 0.25 to 0.38; P < .00001) and platelet engraftment (OR = 0.52; 95% CI, 0.44 to 0.61; P < .00001). PBSCT was associated with a significant increase in the development of grade 3-4 acute graft-versus-host disease (GVHD; OR = 1.39; 95% CI, 1.03 to 1.88) and extensive (47% v 31% at 3 years; OR = 1.89; 95% CI, 1.47 to 2.42; P < .000001) and overall chronic GVHD (68% v 52% at 3 years; OR = 1.92; 95% CI, 1.47 to 2.49; P < .000001), but not grade 2-4 acute GVHD (54% v 53%; P = .49). PBSCT was associated with a decrease in relapse (21% v 27% at 3 years; OR = 0.71; 95% CI, 0.54 to 0.93; P = .01) in both late-stage– (33% v 51% at 3 years; OR = 0.59; 95% CI, 0.38 to 0.93; P = .02) and early-stage– disease patients (16% v 20% at 3 years; OR = 0.69; 95% CI, 0.49 to 0.98; P = .04). Nonrelapse mortality was not different between groups. Overall and disease-free survival were only statistically significantly improved in patients with late-stage disease (overall survival: 46% v 31% at 3 years; OR = 0.64; 95% CI, 0.46 to 0.90; P = .01; disease-free survival: 41% v 27% at 3 years; OR = 0.63 95% CI, 0.45 to 0.87; P = .01).
PBSCT is associated with a decreased relapse rate in hematologic malignancies and improvement in overall and disease-free survival in patients with late-stage disease. PBSCT is also associated with a significant risk of extensive chronic GVHD.
A 20-year-old patient with chronic active EBV infection (CAEBV) received peripheral blood stem cell transplantation (PBSCT) from HLA-one-locus-mismatched mother. Although EB-virus-infected T cells were eliminated after PBSCT, she developed EB-virus-positive B-cell lymphoma of recipient origin in the brain. By reducing the immunosuppressive therapy, the initial lesion disappeared. However, another lesion in the opposite lateral brain appeared later and was resistant to further reduction of immunosuppressive therapy. EBV-DNA was persistently negative after PBSCT in the peripheral blood. This case is suggestive in management of EBV reactivation after SCT and understanding alloimmune response to EBV.
High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n= 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n= 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to (t0), 5 months after (t1) and 9 months after chemotherapy (t2); these parameters were decreased at t1 and t2 compared to t0(high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t1. Paired individual leukocyte samples of t0 and t1 showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to –2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t0 and t1. Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.com
breast cancer; telomere length; high-dose chemotherapy; autologous stem cell transplantation
The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.
Rhabdoid Tumor; Central Nervous System; Drug Therapy; Stem Cell Transplantation; Radiotherapy; Child
The prognosis of patients with de novo myelodysplastic syndromes (MDS), who are red blood cell transfusion-dependent (TD) and receive supportive care is inferior to that of patients not requiring transfusions. It is unknown, whether TD also affects outcome after allogeneic transplantation. We therefore analyzed in 172 de novo MDS patients, median age 51 years, the impact of TD on outcome after high-dose conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT). With a median follow-up of 37 months the probability of 3-year overall survival (OS) did not differ significantly between patients who were or were not TD before PBSCT (p=0.1). However, transfusion burden, as reflected by ferritin levels, correlated with a higher probability of severe acute graft versus host disease (p=0.03) and a higher comorbidity index (p=0.01), and OS was inferior among patients with ferritin levels >1000µg/l before PBSCT (p=0.03). In multivariate analysis only marrow myeloblast count (p=0.01) and comorbidity index (p=0.001) had a significant impact on OS. Thus, these data did not identify TD as an independent negative prognostic factor for outcome after allogeneic PBSCT. However, iron overload, presumably transfusion-related, may contribute to inferior transplant success by adding to the overall comorbidities. Whether clinical intervention in the form of iron chelation would improve results of allogeneic PBSCT in TD patients with MDS remains to be determined.
MDS; transplantation; transfusion; WPSS
In a retrospective study, we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) (n=30) compared with bone marrow transplantation (BMT) (n=110) in children with acute leukemia at 1 year of follow up. Treatment success was defined as disease free survival at one year post transplant. For standard risk disease patients the treatment success rate was 57.1% for PBSCT patients and 80.3% for recipients of BMT (P=NS). The average total cost per treatment success at 1 year in the standard risk disease group was $512,294 for the PBSCT group and $352,885 for the BMT group (P=NS). For patients with high risk disease, the treatment success rate was 18.8% for PBSCT patients and 23.5% for BMT (P=NS). The cumulative average cost for patients in the BMT group was $457,078 compared to $377,316 for PBSCT (P=NS). Point estimates of the incremental cost-effectiveness ratio (ICER) indicate that allogeneic transplantation of bone marrow grafts is dominant over PBSCT for its lower costs and higher effectiveness in patients with standard risk disease (ICER = −$687,108; 95% CI = $2.4 million to dominated). For patients with high risk disease, BMT was more effective and more costly and the ICER was $1.69 million (95% CI = $29.7 million to dominated) per additional treatment success. The comparative economic evaluation provides support for BMT for standard risk patients, but a great degree of uncertainty limits the clear advantage for either treatment option in patients with high risk disease. Further research using larger and randomized controlled trials will be required to confirm the long term cost-effectiveness of each procedure.
children; acute leukemia; allogeneic stem cell transplantation
Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1–167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.
Anaplastic large-cell lymphoma; peripheral blood stem cell transplantation; chemotherapy; anaplastic lymphoma kinase (ALK)
The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Recent data indicated that gamma delta+ T cells might participate in mediating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. However, whether G-CSF could influence the T cell receptors (TCR) of gamma delta+ T cells (TRGV and TRDV repertoire) remains unclear. To further characterize this feature, we compared the distribution and clonality of TRGV and TRDV repertoire of T cells before and after G-CSF mobilization and investigated the association between the changes of TCR repertoire and GVHD in patients undergoing G-CSF mobilized allo-PBSCT.
The complementarity-determining region 3 (CDR3) sizes of three TRGV and eight TRDV subfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using RT-PCR and genescan technique. To determine the expression levels of TRGV subfamily genes, we performed quantitative analysis of TRGVI~III subfamilies by real-time PCR.
The expression levels of three TRGV subfamilies were significantly decreased after G-CSF mobilization (P = 0.015, 0.009 and 0.006, respectively). The pattern of TRGV subfamily expression levels was TRGVII >TRGV I >TRGV III before mobilization, and changed to TRGV I >TRGV II >TRGV III after G-CSF mobilization. The expression frequencies of TRGV and TRDV subfamilies changed at different levels after G-CSF mobilization. Most TRGV and TRDV subfamilies revealed polyclonality from pre-G-CSF-mobilized and G-CSF-mobilized samples. Oligoclonality was detected in TRGV and TRDV subfamilies in 3 donors before mobilization and in another 4 donors after G-CSF mobilization, distributed in TRGVII, TRDV1, TRDV3 and TRDV6, respectively. Signiﬁcant positive association was observed between the invariable clonality of TRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P = 0.015, OR = 0.047).
G-CSF mobilization not only influences the distribution and expression levels of TRGV and TRDV repertoire, but also changes the clonality of gamma delta+ T cells. This alteration of TRGV and TRDV repertoire might play a role in mediating GVHD in G-CSF mobilized allo-PBSCT.
Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC ≤29×109/L), 23 patients (36.5%) in group 2 (PC 30-79×109/L), and 30 patients in group 3 (PC ≥80×109/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.
Thrombocytopenia; Transplantation, Homologous; Allogeneic; Peripheral Blood Stem Cell Transplantation; Mortality; Opportunistic Infections
As long-term survivors of breast cancer after autologous peripheral blood stem cell transplantation (ASCT) are becoming more numerous, studies addressing the issue of long-term follow-up are necessary. In this study, we report on the quality of life (QOL) after ASCT and high-dose chemotherapy (HDCT).
Patients and Methods
The QOL questionnaire version 3.0 by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 version 3.0) was filled in by patients and healthy controls at 5 time points. After obtaining the results, we analyzed the correlation between QOL and the effect factors.
Some functions got significantly worse, and some symptoms got more serious after ASCT and HDCT. However, most of them improved with time and were comparable to the healthy controls after 5 years. QOL was in part related to age, tumor characteristics, educational level, marriage status, and income.
Evaluating QOL allows medical workers to fully understand a patient's state of health, and aid the estimation and selection of clinical treatment methods as well as improve recovery.
Quality of life; Autologous peripheral blood stem cell transplantation; High-risk breast cancer
High-dose chemotherapy (HDCT) with autologous stem cell support has been studied in both the salvage and first-line setting in advanced germ cell tumor (GCT) patients with poor-risk features. While early studies reported significant treatment-related mortality, introduction of peripheral blood stem cell transplantation, recombinant growth factors and better supportive care have decreased toxicity; and in more recent reports treatment-related deaths are observed in <3% of patients. Two to three cycles of high-dose carboplatin and etoposide is the standard backbone for HDCT, given with or without additional agents including ifosfamide, cyclophosphamide and paclitaxel. Three large randomized Phase III trials have failed to show a benefit of HDCT over conventional-dose chemotherapy (CDCT) in the first-line treatment of patients with intermediate- or poor-risk advanced GCT, and to date the routine use of HDCT has been reserved for the salvage setting. Several prognostic models have been developed to help predict outcome of salvage HDCT, the most recent of which applies to both CDCT and HDCT in the initial salvage setting. Patients that relapse after HDCT are usually considered incurable, and additional therapy is provided with palliative intent.
chemotherapy; germ cell tumors; high-dose chemotherapy; stem cell transplantation; testicular cancer
Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.
Myeloid sarcoma (MS); acute myeloid leukemia (AML); allogeneic hematopoietic stem cell transplantation; multidisciplinary team (MDT)
Successful hematopoietic stem cell transplantation (HSCT), both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL) and platelet (>20,000/µL) reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT) and 40 allogeneic bone marrow transplantation (BMT) patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00) and 19.00 (16.00/23.00) and platelet on day 11.00 (10.00/13.00) and 21.00 (18.00/25.00), respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM) and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD) and aplastic anemia (AA) and MM presented the best overall survival (OS) in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR), where CBV, melphalan (M-200) and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.
engraftment; hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; bone marrow transplantation; conditioning regimen
Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34+ cells transplanted during the first and second HDCT/autoSCT were 4.3 × 106/kg (range 0.6-220.2) and 4.1 × 106/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34+ cells was lower, especially if it was < 2 × 106/kg. A lower CD34+ cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34+ cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.
High-Dose Chemotherapy; Autologous Stem Cell Transplantation; CD34+ Cells; Hematologic Recovery; Iron Overload