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A Chaudhry

Publications and source records attributed to A Chaudhry.

At least 19 recordsLinked to original sources
PubMed2006

Overnight storage of autologous stem cell apheresis products before cryopreservation does not adversely impact early or long-term engraftment following transplantation.

To reduce costs and avoid inconvenient overtime work, our institution changed policy in September 2000 so that autologous stem cell apheresis products were stored overnight before cryopreservation rather than immediately processed. This retrospective review was conducted to evaluate the possible impact of this policy change on hematopoietic engraftment following autologous stem cell transplantation (ASCT). In total, 229 consecutive lymphoma patients who underwent a single, unpurged ASCT in Calgary between January 1995 and November 2003 were evaluated. Of these patients, 131 patients' autografts underwent immediate processing and cryopreservation before September 2000, and 98 patients' autografts underwent next-day cryopreservation after overnight storage following this date. Results of univariate and multivariate analyses demonstrated no adverse effect of overnight storage before cryopreservation on the number of days to initial engraftment of platelets or neutrophils, on the proportion of patients with low blood counts 6 months post-ASCT, or on lymphoma relapse rates or overall survival post-ASCT. These data suggest that overnight storage of the autograft before cryopreservation does not adversely affect graft viability or influence long-term disease status, and support the continued use of overnight storage of stem cells before cryopreservation as a convenient, cost reduction measure.

Adolescent↗
PubMed2006

Notch3 signaling initiates choroid plexus tumor formation.

Notch3 has been studied in the context of brain development, but whether it plays a role in the formation of brain tumors is unclear. We demonstrate that the introduction of constitutively active Notch3 into periventricular cells of embryonic day 9.5 mice causes the formation of choroid plexus tumors (CPTs). Tumors arose in the fourth ventricles in 83% of animals and were associated with hydrocephalus. They were microscopically highly similar to choroid plexus papillomas in humans, with an ongoing proliferation rate of 4-6%. Signs of Notch pathway activity were also present in human choroid plexus lesions, and receptor mRNA levels in papillomas were elevated over those in non-neoplastic choroid plexus. Notch2 was overexpressed approximately 500-fold in one case, suggesting that the role of this pathway in CPTs may not be specific to Notch3. Our findings indicate that activated Notch3 can function as an oncogene in the developing brain, and link the Notch pathway to human CPT pathogenesis.

Animals↗
PubMed2006

IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis.

Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection, unresolving inflammation and progressive lung damage. Bronchiectasis can be associated with autoimmune diseases including ulcerative colitis. Defects of both innate and adaptive immunity have been proposed. The airway inflammation is characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils and T cells. Here we investigated two candidate gene polymorphisms that may contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that is implicated in IL-8 binding and neutrophil trafficking as well as the interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of IFNgamma production. These polymorphisms were distributed similarly in the idiopathic bronchiectasis group and controls, suggesting that these two candidate gene polymorphisms are not associated with disease susceptibility.

Alleles↗
PubMed2005

Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience.

Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of >10%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status.

Adult↗
PubMed2005

Evaluation of the mutagenic potential of chlorpyrifos (CPF) using polytene chromosomes of Anopheles mosquito.

Diverse cytogenetic tests are employed for short term screening of suspect environmental mutagens by using insects and mammals as models. In the present paper the polytene chromosomes of a mosquito Anopheles maculatus were used to evaluate the mutagenic potential of a widely used organophosphate pesticide chlorpyrifos-[o, o-diethyl-o-(3, 5, 6-trichloro-2-pyridyl) phosphothioate]. The results are based on the frequency of various structural aberrations encountered in the polytene chromosomes of the larvae treated with LC20 of chlorpyrifos (CPF). These aberrations were dominated by inversions, stickiness of the chromosomes, heterochromatinization of the bands and lack of polyteny. The frequency of various aberrations was highest in the left arm of chromosome number 2L followed by 2R, 3L, 3R, and X-chromosomes i.e. 2.10 +/- 0.44, 1.84 +/- 0.44, 1.57 +/- 0.54, 1.31 +/- 0.50, and 0.22 +/- 0.27 respectively. The susceptibility of different chromosomal arms to this pesticide was 2L > 2R > 3L > 3R > X and the regions prone to these aberrations have been marked on the polytene chromosome map of Anopheles maculatus.

Animals↗
PubMed2003

High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma.

Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS) 60 years, or relapsed disease. All but one patient tolerated the treatment well and experienced improvements in neurological function and overall performance status post-transplant. No treatment-induced neurotoxicity (dementia, ataxia, and incontinence) was observed although the follow-up is short. One early treatment-related death occurred in a patient with multiple comorbid medical conditions. The other six patients achieved a complete response (CR) after TBC and ASCT. Five patients are currently alive and relapse-free at 5, 8, 24, 36, and 42 months from diagnosis. One additional patient relapsed and died 33 months after diagnosis. Two of the seven patients received TBC/ASCT as the only treatment after disease progression following their initial chemotherapy and both remain relapse-free at the time of this report, 22 and 31 months post-TBC/ASCT. In conclusion, prolonged CR can be attained after chemotherapy-only treatment of poor prognosis PCNSL. Furthermore, this small series suggests that high-dose chemotherapy for PCNSL should include drugs that penetrate the CNS such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.

Adolescent↗
PubMed2002

Successful treatment of post-transplant lymphoproliferative disorder in autologous blood stem cell transplant recipients.

We report three cases of post-transplant lymphoproliferative disorder (PTLD) in the context of autologous stem cell transplantation (ASCT) for multiple myeloma (MM) and non-Hodgkin's lymphoma. The first two cases received ASCT for MM, one with a CD34-selected autograft and the other with an unmanipulated autograft. Both these cases of PTLD achieved a complete response following treatment with IVIG, gancyclovir, solumedrol and interferon (IFN). The third case received ASCT with an unmanipulated autograft for relapsed angioimmunoblastic lymphoma. He also achieved a complete response but only after rituximab was added to IVIG, gancyclovir, solumedrol and IFN. None of these patients experienced a relapse of their PTLD with follow-up ranging from 1.5 to 5 years. These cases highlight the importance of considering PTLD in the differential diagnosis of lymphadenopathy and fever post ASCT. They also demonstrate the possibility of durable complete remission of post-ASCT PTLD following antiviral and immune modulating therapy.

Adult↗
PubMed2002

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis.

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.

Antilymphocyte Serum↗
PubMed2002

Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma.

In an attempt to improve the dismal prognosis of adults with recurrent medulloblastoma, six patients were treated with aggressive salvage therapy including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). At relapse, all patients underwent surgical debulking followed by HDCT/ASCT and then radiotherapy when possible. The treatment plan included two cycles of HDCT/ASCT; first with cyclophosphamide, etoposide and carboplatin (CECb) and then 2 months later with cyclophosphamide and thiotepa (CT). Three of the six patients received the planned therapy. One patient experienced severe toxicity requiring life-sustaining therapy. This patient developed multi-organ dysfunction including multiple enhancing lesions in both cerebral hemispheres that slowly resolved over several months. Two other patients did not mobilize sufficient stem cells for two ASCT procedures. They received one ASCT conditioned with cyclophosphamide, thiotepa and carboplatin (CTCb). Three of six patients had a complete response (CR); the other three had a partial response (PR). Following the first ASCT, median duration of response was 13.5 months (range 9-29 months) and median survival was 21.5 months (range 12-42 months). There was no treatment-related mortality. We conclude that HDCT/ASCT with CECb-CT or CTCb is active against recurrent medulloblastoma in adults and may be associated with prolonged remissions. Multiple enhancing cerebral lesions on brain MRI early post-HDCT/ASCT may be a consequence of the treatment rather than metastatic disease.

Adult↗
PubMed2002

Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes.

The availability of an i.v. form of busulfan (Bu) has prompted investigation of administration schedules other than the 4-times-daily dosage commonly used with oral Bu. We have studied an allogeneic stem cell transplantation (SCT) preparative regimen comprising fludarabine (FLU) 50 mg/m2 on days -6 to -2 plus i.v. Bu 3.2 mg/kg daily in a 3-hour infusion on days -5 to -2. The regimen was given to 70 patients aged 15 to 64 years (median, 41 years) with hematologic malignancy. Thirty-six patients (51%) had high-risk malignancy, 28 (40%) had unrelated or genotypically mismatched related donors (alternate donors [AD]) and 29 (41%) received bone marrow rather than blood as stem cell source. Acute GVHD prevention comprised antithymocyte globulin 4.5 mg/kg over 3 days pretransplantation, cyclosporin A, and short-course methotrexate with folinic acid. Hepatic toxicity was transient and there was no clinically diagnosed veno-occlusive disease. Grade II stomatitis occurred in 49 patients (70%) and hemorrhagic cystitis in 9 patients (13%). One patient with subtherapeutic phenytoin levels had a convulsion 8 hours after the third i.v. Bu dose, but no other neurotoxicity was apparent. Incidence of acute GVHD grades II to IV was 8% and incidence of grade III-IV was 3%, with no deaths from this cause. Actuarial incidence of chronic GVHD at 2 years is 38%. There were 2 cases of graft failure in unrelated donor BMT recipients, 1 of which was reversed by asecond transplantation. With a median follow-up of 16 months (range, 6-27 months), transplantation-related mortality at 100 days and 2 years was 2% and 5% for matched related donor (MRD) SCT and 8% and 19% for AD SCT, respectively (P = not significant). Relapse rates were 21% for 34 patients with acute myeloid leukemia (AML) in complete remission or chronic myeloid leukemia in chronic phase (low-risk), 66% for 19 patients with high-risk AML, and 18% for 17 patients with other active malignancy. Projected disease-free and overall survival rates at 2 years were 74% and 88% for low-risk disease, 26% and 37% for advanced AML, and 65% and 71% for other high-risk disease, respectively. Pharmacokinetic studies were done using 11 samples with the first and fourth doses of Bu. Kinetics were linear, and for the first and fourth doses, the half-lives were 2.60 +/- 0.44 and 2.57 +/- 0.36 hours, respectively. Clearances were 106.77 +/- 16.68 and 106.86 +/- 21.57 mL/min per m2, peak concentrations (Cmax) were 3.92 +/- 0.31 and 3.96 +/- 0.28 mcg/mL, and Bu areas under the plasma concentration versus time curve (AUC) were 4866.51 +/- 771.42 and 4980 +/- 882.80 microM x min, respectively. Bu was completely cleared within 24 hours and the day 4 pharmacokinetic values were very similar to those on day 1 for every patient. The cumulative AUC was comparable to the target range established for p.o. Bu. This regimen incorporating once-daily i.v. Bu is convenient to give, is relatively well tolerated, gives predictable blood levels, and deserves further study in circumstances in which cytoreduction as well as immune suppression is needed.

Adolescent↗
PubMed2001

Role of residues constituting the 2beta1 strand of domain II in the biological activity of anthrax protective antigen.

Anthrax toxin consists of three proteins, protective antigen, lethal factor and oedema factor. A proteolytically activated 63-kDa fragment of protective antigen binds lethal factor/oedema factor and translocates them into the cytosol. Domain II of protective antigen has been implicated in membrane insertion and channel formation. In the present study, alanine substitutions in 14 consecutive residues of the 2beta1 strand that are highly homologous to the putative membrane interacting segment of Clostridium perfringens iota-b toxin were generated and the effect on the biological activity of protective antigen studied. One of the mutants, Pro260Ala, showed considerably reduced toxicity in combination with lethal factor. The mutant also showed decreased membrane insertion and translocation of lethal factor into the cytosol. The data suggest that Pro260 is important for membrane insertion and translocation by protective antigen.

Animals↗
PubMed2001

The CD3- 16+ 56+ NK cell count independently predicts autologous blood stem cell mobilization.

Better predictive factors for autologous blood stem cell mobilization (BSCM) are needed. The purpose of this study was to determine if an independent association exists between lymphocyte or NK cell counts and BSCM. Data were analyzed on 141 consecutive patients aged 19-69 years (median 45) who received combined chemotherapy plus G-CSF for BSCM, and who had measurements of immune cells prior to BSCM. Of the 141 patients, 41% had breast cancer, 14% Hodgkin's disease, 34% non-Hodgkin's lymphoma, and 11% other diagnoses. BSCM involved dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP) plus G-CSF 300 microg (<70 kg) or 480 microg (>70 kg) for 45% of patients, while the remaining 55% received other chemotherapy plus similar doses of G-CSF. Only a single apheresis was performed for 94% of patients. The following factors were analyzed for predictors of BSCM: age, gender, prior chemotherapy, prior radiotherapy, diagnosis, disease status, marrow involvement, mobilization regimen, Hb, WBC, platelet count, B cell, T cell, and NK cell counts. The peripheral blood CD34+ counts on the first day of apheresis (PBCD34) were 6-1783 x 10(6)/l (median 150). The PBCD34 count correlated strongly with the number of CD34+ cells collected/l blood apheresed and with the number of CD34+ cells collected/kg. By multivariate analysis using continuous variables, relapsed status (P = 0.0003), not using DICEP mobilization (P = 0.0001), female gender (P = 0.0057), low platelet count (P = 0.051), and low CD3- 16+ 56+ count (P = 0.0158) were associated with low PBCD34 counts. Using categorical variables, the only factors that independently predicted a PBCD34 count <150 x 10(6)/l were: >1 prior chemotherapy regimen (odds ratio = 5.12, P = 0.0003), not using DICEP mobilization (odds ratio = 4.94, P = 0.0001), and CD3- 16+ 56+ count <125 x 10(6)/l (odds ratio= 2.58, P = 0.0157). In conclusion, the CD3- 16+ 56+ count may be a useful additional predictor of BSCM and warrants further study.

Adult↗
PubMed2001

A novel potent antagonist of peroxisome proliferator-activated receptor gamma blocks adipocyte differentiation but does not revert the phenotype of terminally differentiated adipocytes.

The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Their antihyperglycemic effects seem to be linked to the regulation of PPARgamma-responsive genes. Here, we report the characterization of a specific PPARgamma antagonist that blocks several of the biological activities of the PPARgamma agonist rosiglitazone. PD068235 inhibited rosiglitazone-dependent PPARgamma transcriptional activity with an IC(50) of 0.8 microM and rosiglitazone-stimulated in vitro coactivator association. The role of PPARgamma in the initiation of differentiation is well documented. In this study, we used PD068235 as a tool to evaluate the functional role of PPARgamma in the maintenance of the terminally differentiated state. Treatment of confluent, growth-arrested 3T3-L1 preadipocytes with PD068235 blocked adipocyte differentiation induced by the standard adipogenic hormonal mixture (insulin/dexamethasone/isobutylmethylxanthin) and fully antagonized rosiglitazone-induced adipogenesis. In contrast, long-term treatment of terminally differentiated 3T3-L1 adipocytes with PD068235 did not induce any obvious morphological changes and had no effect on basal lipolysis rates. In addition, in fully differentiated adipocytes PD068235 did not alter the basal expression of PPARgamma target genes aP2 and CAP, but it effectively blocked rosiglitazone-induced expression of both genes. These results suggest that in terminally differentiated adipocytes, the PPARgamma activity is minimal and may not be required for the maintenance of PPARgamma target gene expression.

3T3 Cells↗
PubMed2001

Contour interaction for an easily resolvable stimulus.

It is well known that adjacent contours can reduce the visual acuity of single letters. Although this has traditionally been considered only in terms of a neural-based interaction, it has recently been suggested that the information content in the stimulus may account for the interaction. Here we ask the question, "Do similar interference effects occur for the discrimination of low-contrast letters whose size is larger than that corresponding to the resolution limit?" If so, previous acuity-based interaction results may be of more general importance. We show that while there are interference effects of nearby contours, they are of a form different from that observed at the resolution limit. In particular, the contrast polarity of the nearby contour is unimportant, which in turn suggests that a physical explanation is inappropriate. Also, the discrimination of an easily resolvable, unflanked Landolt C target requires information over a much wider spatial-frequency range than its counterpart at the resolution limit.

Discrimination, Psychological↗
PubMed2000

Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience.

Although it is common practice to use some form of isolation to protect allogeneic stem cell transplant patients from infection, the necessity for these practices in all environments has not been demonstrated. The current study evaluated patterns of infection and 100-day transplant-related mortality in 288 patients with myelodysplasia and leukemia transplanted without isolation. Patients were allowed out of hospital at any time within constraints of the medication schedule. Fever, foci of infection, and positive cultures within 28 days and death within 100 days because of the transplant procedure were recorded. Fever occurred in 57% of patients, and 10% had a clinical or radiographic focus of infection. Most infections were apparently endogenous; blood cultures from 24% of recipients grew organisms, 87% of which were gram-positive bacteria. Four patients (1%) died with aspergillus infection in circumstances indicating that isolation would not have been helpful. Twenty percent of patients remained without evidence of infection throughout. Transplant-related mortality at 100 days was 1% for 108 patients with early leukemia receiving transplants from matched siblings. For patients at higher risk, by virtue of donor and/or disease status, mortality was 21%. These figures compare favorably with those reported to the International Bone Marrow Transplant Registry, the majority of patients having been subjected to some form of isolation. We conclude that allogeneic stem cell transplantation can be safely performed in some environments without confining patients continuously to the hospital.

Adolescent↗
PubMed2000

The CD34+90+ cell dose does not predict early engraftment of autologous blood stem cells as well as the total CD34+ cell dose.

CD90 or Thy-1 is an antigen co-expressed with CD34+ on putative immature hematopoietic stem cells. Peak mobilization of CD34+90+ cells into the blood occurs a few days earlier than peak mobilization of total CD34+ cells. Because it is not known which cell type best correlates with engraftment, the optimal timing of apheresis remains unclear. The purpose of the study was to determine if the CD34+90+ cell dose predicts engraftment of autologous blood stem cells independent of the total CD34+ cell dose/kg, the dose of other CD34+ cell subsets (CD34+33-, CD34+38-, CD34+41+), or various clinical factors. Data were analyzed on 125 consecutive patients ranging in age from 19 to 66 years (median 46) who underwent autologous blood stem cell transplantation (ABSCT) for breast cancer (54), lymphoma (59), or other malignancies (12). By univariate analysis, neutrophil (> or = 0.5 x 10(9)/l) and platelet (> or = 20 x 10(9)/l or > or = 100 x 10(9)/l) engraftment correlated better with the total CD34+ cell dose than with the CD34+90+ cell subset. Using Cox proportional hazards models, factors independently associated with both neutrophil engraftment (> or = 0.5 x 10(9)/l) and platelet engraftment (> or = 20 x 10(9)/l and > or = 100 x 10(9)/l) were higher total CD34+ dose/kg and high-dose regimen (melphalan-containing slower than other regimens). In conclusion, the total CD34+ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34+ subset, including CD34+90+ cells. Apheresis should continue to be timed according to peak CD34+ levels.

Adult↗
PubMed2000

Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior to high-dose melphalan and autologous stem cell transplantation.

We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) HD. DICEP re-induction and blood stem cell mobilization was used for 21 patients. Factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, B symptoms at relapse, bulk, post-ASCT radiotherapy, and DICEP re-induction therapy. Cox proportional hazards models were constructed for both event and death. DICEP and HDM were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. For all 46 patients, the projected 5 year EFS was 52% (95% CI = 38-72%) and OAS was 57% (95% CI = 40-82). Factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). Factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), > or =3 prior chemotherapy regimens (RR = 4.72, P = 0.019), and not using DICEP (RR = 7.49, P = 0.015). This study demonstrates that DICEP re-induction prior to HDM/ASCT is feasible. The preliminary data are sufficiently encouraging to warrant a multicenter phase II or a phase III trial evaluating DICEP followed by HDM/ASCT as salvage therapy for HD.

Adolescent↗