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Background: Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT)., Patients: Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance., Results: Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum β2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008)., Conclusion: In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described., Patients and Methods: HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered., Results: Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients., Conclusion: A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications., (© 2014 by American Society of Clinical Oncology.)

Background: We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome., Patients and Methods: Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT., Results: 43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS., Conclusions: These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

Bortezomib-based regimens have significant activities in multiple myeloma (MM). In this study, we tested the efficacy of a total therapy with a staged approach where newly diagnosed MM patients received vincristine/adriamycin/dexamethsone (VAD). VAD-sensitive patients (> or =75% paraprotein reduction) received autologous hematopoietic stem cell transplantation (auto-HSCT), whereas less VAD-sensitive patients (<75% paraprotein reduction) received bortezomib/thalidomide/dexamethasone (VTD) for further cytoreduction prior to auto-HSCT. On an intention-to-treat analysis, a progressive increase of complete remission (CR) rates was observed, with cumulative CR rates of 48% after HSCT. Seven patients progressed leading to three fatalities, of which two had central nervous system disease. The 3-year overall survival and event-free survival were 75.1% and 48.3%, respectively. Six patients developed oligoclonal reconstitution with new paraproteins. In the absence of anticoagulant prophylaxis, no patients developed deep vein thrombosis. The staged application of VAD+/-VTD/auto-HSCT resulted in an appreciable response rate and promising survivals. Our approach reduced the use of bortezomib without compromising the ultimate CR rate and is of financial significance for less affluent communities.

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, x3; mitoxantrone 10 mg/m2/d, x1; dexamethasone 20 mg/d, x5; monthly cycles, x6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50.5%, 18% and 68.5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37.5%, P = 0.03; OR: 84% vs. 47.5%, P < 0.001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0.039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0.001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0.001) and OS (67 months vs. 13 months, P < 0.001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.

The optimal treatment of acute promyelocytic leukaemia (APL) recurring from relapses successfully treated using arsenic trioxide (As2O3) is undefined. Three APL patients relapsing from As2O3-induced remission were studied. Re-treatment with As2O3 failed in one patient in third relapse, and resulted in morphological but not molecular remission in another patient. Combination therapy with As2O3 and all-trans retinoic acid (ATRA), however, resulted in morphological and molecular remission in all three cases, with a follow-up time ranging from 6 to 16 months. Our results suggest a synergistic therapeutic effect between As2O3 and ATRA in APL in advanced relapse.

Background: Small patient numbers and short follow-up are common in some acute myeloid leukaemia (AML) studies and data on secondary malignancies after treatment of AML are rare., Aims: To determine the prognostic factors and long-term treatment results., Methods: A retrospective study of patients with de novo AML under the age of 60 over a 20-year period in which two induction therapy regimens: 7:3 (1975-1983) and 7:3:7 (1984-1996) and three consolidation chemotherapy regimens: 5:2 (1975-1983), 5:2:5 (1984-1990) and Ara-C/mitoxantrone (1991-1996) were used. Disease-free (DFS), overall survivals (OS) and prognostic factors were analysed., Results: Two-hundred and two of 276 (73%) patients attained complete remission (CR). The CR rates of 7:3 and 7:3:7 regimens were 70.5% and 74.5% respectively (p=0.92). The median DFS was 12 months and the projected DFS at 10- and 20-years were 23% and 21% respectively. For patients consolidated with 5:2, 5:2:5 and Ara-C/mitoxantrone, the median DFS was 15 m, 12 m and 11 m respectively and the projected ten-year DFS were 27%, 21% and 18% respectively (p=0.2). Ninety per cent of relapses occurred within two years from remission but there were two late relapses at 109 m and 120 m respectively. Young age and FAB M3 subtype were favourable prognostic factors to OS (p=0.04) and DFS (p=0.006) respectively. There was no secondary solid tumour in the long-term survivors., Conclusion: Our experience confirmed the efficacy of standard-dose Ara-C/daunorubicin and the prognostic value of age and FAB subtype. Median and projected DFS were similar to western studies.

We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13-59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty-five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP-ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease-free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients., (Copyright 1999 Wiley-Liss, Inc.)

For 10 consecutive patients in our unit who did not show a significant rise in blood progenitor cells within 14 days following chemotherapy and G-CSF, we increased the G-CSF dose from 5 to 10 microg/kg/day (n = 9) or from 10 to 15 microg/kg/day (n = 1). As a result, there were significant increases in total yield as well as yield per apheresis of mononuclear cells, CD34+ cells and CFU-GM (P < 0.025, <0.01 and <0.005, respectively). After G-CSF dose escalation, six of the 10 patients had sufficient CD34+ cells for performing transplantation. These results demonstrate a dose-dependent response of progenitor cell mobilization by G-CSF when used in combination with chemotherapy. Moreover, increasing the dose of G-CSF as late as the third week of mobilization may still provide sufficient cell yield even with patients who did not show a significant mobilization with conventional doses of G-CSF.

From 1991 to 1997, we have treated 78 newly diagnosed patients with aggressive non-Hodgkin's lymphoma with a modified CHOP regimen in which epirubicin (60 mg/m2) was used in place of doxorubicin (50 mg/m2), i.e. CEOP (cyclophosphamide, epirubicin, vincristine and prednisolone). The median age was 41 years (range: 17 to 67). Sixty-four (82 per cent) had diffuse large cell (Working Formulation category G) histology. The median LDH level was 453 u/l. Thirty-three (42.3 per cent) and 45 (57.7 per cent) had stage I/II and stage III/IV disease, respectively. Fifty-five of 78 (71 per cent) CEOP-treated patients achieved CR, and the projected DFS and OS were both 65 per cent. In an earlier cohort of patients (from 1985-1991) treated with second or third-generation chemotherapy regimens (m-BACOD, MACOP-B, ProMACE-CytaBOM), CR was achieved in 95/123 (77 per cent) patients and the projected DFS and OS were 62 per cent and 55 per cent. There was no significant difference in the clinical characteristics, CR rates (p = 0.26), DFS (p = 0.38) or OS (p = 0.68) between patients who received CEOP or second/third-generation chemotherapy regimens. Of the patients treated with CEOP, 37.9 per cent, 28.8 per cent, 24.2 per cent and 9.1 per cent were in the age-adjusted International Index L, LI, HI and H risk groups, with CR rates of 82 per cent and 57 per cent in the L/LI and HI/H risk groups (p = 0.03). Moreover, patients in the L, LI and HI/H risk groups had significantly different projected DFS (87 per cent, 62 per cent and 39 per cent, p = 0.02) and OS (85 per cent, 80 per cent and 36 per cent, p = 0.006). In conclusion, CEOP is an effective regimen and the age-adjusted International Index is valid for Chinese patients with aggressive NHL.