Search

Unlabelled: Clinical studies have shown that patients with chronic myeloid leukaemia (CML) treated with allogeneic bone-marrow transplantation (BMT) experience not only prolonged disease-free survival but also complete cure in some. Therefore, we followed a cohort of 81 Chinese patients who received allogeneic BMT., Patients and Methods: The donors were either relatives (65 siblings, 1 parent) or unrelated volunteers (15). BMT was performed at a median interval of 11.6 months from diagnosis of CML, and the stages of disease before BMT were: first chronic phase (60 patients), accelerated or second chronic phase in (10 patients), and blastic crisis (11 patients). Three conditioning regimens were employed: Bu-Cy, Cy-TBI, or Bu-Cy-TBI. Standard cyclosporin and short methotrexate protocol were used for acute graft-versus-host disease (GvHD) prophylaxis., Results: There were five graft failures with three after related BMT. Patients after related or unrelated BMT had a comparable rate of neutrophil recovery (median = 22 days), but significant delay in platelet recovery occurred after unrelated BMT (median = 34 vs. 20 days, P < 0.05). The latter also had higher incidence of acute GvHD (73% vs. 41%, P < 0.05), although the incidence of chronic GvHD was not different between groups. At a median follow-up of 43.5 months, patients after related BMT had a significantly better rate of disease-free survival (68% vs. 37.3%, P < 0.05) and overall survival (81% vs. 38.9%, P < 0.05) at 4 years. Subgroup analysis of patients after related BMT showed the outcome was better when they were transplanted at first chronic phase. Multivariate analysis showed that advanced disease (RR = 2.01, 95% CI = 1.48-2.73) significantly worsened the outcome of BMT, whereas the presence of chronic GvHD had a protective effect against relapse and survival (RR = 0.09, 95% CI = 0.02-0.38)., Conclusion: Allogeneic BMT is a curative form of treatment for patients with CML. Treatment outcome is best for those who undergo transplants from HLA-matched siblings during the first chronic phase.

We describe a patient with primary anaplastic large cell lymphoma of the forearm presenting with compartment syndrome. Urgent decompression fasciotomy and combination chemotherapy resulted in durable remission status. This is followed by a review of primary skeletal muscle lymphoma in the English literature.

We report the clinical, molecular, and immunohistological findings of 20 Chinese patients with mantle cell lymphoma diagnosed over a 10-year period. The disease affected mainly elderly patients (median age, 65.5 years) with a male predominance (M/F, 3/1). Eighty percent presented with advanced stage III/IV disease but only 25% had B symptoms. Eighty-five percent had extranodal disease at presentation. Complete remission (CR) and partial remission (PR) were achieved in 45% and 40% of the patients, respectively. There was no difference in the CR rate for patients treated with anthracycline-containing or nonanthracycline-containing regimens (43% and 50%, P = 0.67). Disease progression or relapse was observed after a median of 26 months in patients who initially responded to treatment. Extranodal relapse occurred in the central nervous system (n = 1), bone marrow (n = 1), pleura (n = 2), orbit (n = 2), and the gastrointestinal tract (n = 3). The median overall survival (OS) was 52 months but there were no long-term survivors. This was not different from the median OS of 53 months of patients with diffuse large cell (DLC) lymphoma treated in the same center over the same period (log rank, P = 0.76). Of the 12 patients who were tested for bcl-1 rearrangement by polymerase chain reaction (PCR), five (42%) were positive for rearrangement in the major translocation cluster (MTC) region. The median OS rates were 45 months and 63 months for PCR positive and negative patients, respectively (P = 0.97). In conclusion, MCL is a disease mainly of the elderly in the Chinese with a male predominance and most had advanced-stage disease and extranodal involvement at presentation. Clinicopathologic features and treatment outcome were similar to Caucasian patients, in that the disease combined the aggressive nature of DLC lymphoma and the incurability of low-grade lymphoma.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.

We report a case of fungal endocarditis due to Aspergillus terreus in a leukaemia patient who received a bone marrow allograft from a matched unrelated donor. He presented with persistent fever. microangiopathic haemolytic anaemia but there was no cardiac signs and symptoms. He died despite intravenous amphotericin B. Review of the English literature showed five other patients with fungal endocarditis in the setting of bone marrow transplantation and revealed the same features of difficult diagnosis and poor outcome.

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.

We report a case of primary CD30-positive anaplastic large cell lymphoma of the lip. While extranodal involvement is not uncommon in Ki-1(CD30) anaplastic large cell lymphoma, this is the first reported case of primary lip involvement. The clinical features and clinical outcome in Ki-1 anaplastic large cell lymphoma are discussed.

Severe aplastic anemia (SAA) is a disease associated with high mortality. For young patients with HLA identical siblings, allogeneic bone marrow transplantation (BMT) offers the best chance of cure. Favourable results have also been reported using immunosuppressive therapy (IST). Transplantation is usually favoured for patients below 45 years of age. We report our experience of 11 allogeneic and one syngeneic BMT for adult Chinese patients with SAA, over a 4-year period from 1991 to 1995. Ten of the 12 (83 per cent) patients had received and failed prior IST including anti-thymocyte globulin (ATG) before being referred for BMT. Neutrophil and platelet engraftment was successful in 11 of them (92 per cent) and nine were completely transfusion independent after transplantation. Their overall 3-year survival was 67 per cent. The compromised overall result was due to a number of cases transplanted after a long time delay. No patient transplanted beyond 3 years from the initial time of diagnosis of SAA achieved long-term marrow engraftment, and they all eventually succumbed. On univariate analysis, a longer time delay and hence a larger amount of blood products exposure, were highly significantly statistically associated with inferior marrow engraftment and patient survival. Other factors including age, iron status, infused cell dose and the conditioning protocol were not found to significantly affect engraftment and survival. Graft versus host disease was clinically mild or absent in most patients. This may be related to ethnicity or previous ATG exposure. In conclusion, early allogeneic BMT was a safe and effective treatment in our small series of patients with SAA failing IST.

A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5' end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.

A case of non-Hodgkin's lymphoma with features mimicking that of multiple myeloma is reported. A 67-year-old man presented with lymphadenopathy and the classic constellation of symptoms and signs of multiple myeloma, including generalised bone pain, hypercalcemia and multiple osteolytic lesions on the skeletal survey. However, cervical lymph node biopsy showed diffuse large cell lymphoma and marrow aspirate showed infiltration with lymphoma cells different in both morphology and surface markers to myeloma cells.

A 37-year-old untransfused, non-drinking man with Hemoglobin H-CS disease presented with insulin-dependent diabetes mellitus, markedly elevated serum ferritin level, and marked iron deposition in hepatocytes. He did not carry either of the two common mutations of the HLA-H gene for hereditary hemochromatosis, namely, Cys282Tyr and His68Asp, nor did he have the associated HLA marker (HLA-A3, B7 nor B-14) for the disease. Patient with HbH disease should be monitored for iron overload.

A patient with light chain myeloma complicated by simultaneous Herpes simplex and Aspergillus fischeri pneumonia is presented. Microscopic examination of her bronchoalveolar specimen showed bronchial cells with cytopathic effects and numerous cleistotheca, the sexual reproductive structures of Aspergillus. Culture was positive for Herpes simplex virus and Aspergillus fischeri. The initial partial response to amphotericin B followed by complete clinical response with addition of intravenous acyclovir emphasized the importance of recognition of simultaneous infection by these 2 pathogens. This is the first report of identifying cleistotheca in the bronchoalveolar lavage specimen.

Forty-one patients with polycythemia vera (PV) according to the PVSG criteria were analysed retrospectively from January 1960 to March 1996. There were 23 male and 18 female patients with a median follow-up of 66.5 months (3-431 months). Median age was 62 (range: 37-85). The median hemoglobin level at diagnosis was 18.8 g/dl. Four patients were treated by venesection alone, 20 patients received hydroxyurea and intermittent venesection, 3 were treated with radioactive phosphorus alone, and 14 had both hydroxyurea and radioactive phosphorus. During the course of illness, 14 patients (34%) developed a total of 19 thrombotic events. Of the thrombotic events, 16 were arterial and 3 were venous. Two patients had both arterial and venous thrombosis sequentially. The probability of thrombosis-free survival after treatment was 83% at 10 years and 73% at 20 years. One patient developed post-polycythemic myeloid metaplasia 24 months after diagnosis. Of 17 patients exposed to radioactive phosphorus, only 1 developed secondary acute myeloid leukemia (AML) 9 years afterwards. Of the 20 patients treated with hydroxyurea for a median duration of 63.5 months (2-130 months), there is no case of secondary malignancy. Overall survival was 83% at 10 years and 62% at 20 years. In conclusion, PV in Chinese is a relatively benign disease with a low risk of thrombosis as compared to Caucasian patients. Hydroxyurea has a very low risk of secondary leukemia and is a safe drug to use in Chinese patients with PV.

The surface molecule CD56 marks a category of malignant lymphoma of putative natural killer (NK) cell origin. We conducted a retrospective analysis of 24 cases of CD56+ NK lymphoma/leukaemia to define the clinicopathologic and prognostic features of this specific group of lymphomas. 56 cases of nasal lymphomas and 204 cases with an initial diagnosis of peripheral T-cell lymphoma were retrospectively analysed. To specifically examine lymphomas of putative NK origin, only those that were negative for surface expression of CD3 but positive for CD56 were analysed. 24 cases were identified. The initial predominant sites of involvement were nasal (n = 18), palate (n = 1), nodal (n = 1) and multi-organ (n = 4). Clinically, in patients with disease localized to one anatomical site (n = 20), most had symptoms confined to the nose, with a high percentage in early stage (I: 91%; IV: 9%). The marrow was not involved in any of these cases. However, patients with multi-organ involvement at presentation (n = 4) behaved differently. All presented acutely with pancytopenia, hepatosplenomegaly, and marrow infiltration with haemophagocytosis. A leukaemic phase was observed in one case. Anthracycline containing combination chemotherapy resulted in complete remission in 75% of patients with localized disease, but only in 25% with multi-organ involvement. The median survival of patients with localized disease was 12 months, compared with 2 months in the multi-organ group (P = 0.06); the disease-free survival was significantly better in the former (P < 0.01). The overall median survival of all patients was still poor at 11 months. We conclude that CD56+ NK lymphomas could be divided into two main patterns of disease presentations: localized (predominantly nasal), and multi-organ involvement. Each has different clinicopathologic and prognostic features. Conventional chemotherapy appeared ineffective for the majority of patients, and innovative treatment modalities are needed to improve outcome.

Thirty-nine consecutive patients with acute lymphoblastic leukemia were treated with an intensive chemotherapy protocol. There were 23 males and 16 females with a median age of 37 years (range: 15-65). Eighteen patients had common ALL, seven had pre-B ALL, three early-precursor B ALL, seven T-ALL and four had aberrant expression of myeloid antigens (c-ALL in three and pre-B ALL in one). The median initial leukocyte count was 11.8 x 10(9)/l (range: 0.65-295). Cytogenetic result of the marrow was available in 16 of 39 patients (41 per cent) and showed Philadelphia positivity in six, a normal result in six and one each of t(4,11), t(1,19), hyperdiploidy and del 12p. Hepatosplenomegaly was present in about 20 per cent of the patients. L-Asparaginase-related hepatic toxicity was the commonest toxicity (48.7 per cent) during phase I of induction. Prolonged pancytopenia and hypoplastic death were common during phase II. With the use of growth factors during the neutropenic period of phase II induction, the rate of hypoplastic death was reduced from 40 per cent to 3 per cent. Common causes of treatment failure included early hypoplastic death (27.8 per cent) and leukemia relapses (50 per cent) while primary refractory leukemia, hepatic failure and perforated peptic ulcer contributed to 11.1, 5.5 and 5.5 per cent of the other deaths. A high complete remission (CR) rate (87.4 per cent) was achieved after phase I induction. The median event-free survival (EFS) was 8 months and the 3-year event-free survival was 43 per cent. This result compared favourably to the other regimens previously employed in our institution. In conclusion, satisfactory survival can be achieved with this intensive regimen. Good supportive care was however, essential to minimize toxicities.

Primary cardiac lymphoma is a rare entity. We report on the clinicopathological features of 2 patients with primary cardiac lymphomas: one involving the right atrium resulting in intractable right heart failure, and the other involving the pericardium with massive pericardial effusion. In the first patient, sternotomy and surgical biopsy of the tumor were performed to arrive at the diagnosis. In the second patient, CT thorax and transesophageal echocardiography helped to diagnose the pericardial tumor, and cytological examination of the pericardial fluid established the pathological diagnosis of lymphoma. Combination chemotherapy (COPP) was started in both patients. The first patient died on the first day of chemotherapy due to intractable heart failure, while the second attained a partial response to chemotherapy but died of progressive disease 8 weeks later. This is followed by a literature review of 21 patients with primary cardiac lymphoma. In conclusion, the prognosis of primary cardiac tumor remains poor.

Primary B cell mediastinal lymphoma has been recognized as a distinct entity recently. This is a retrospective study to define the clinical features and treatment outcome over a 10-year period. Twenty-four consecutive patients (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum were studied. The median age was 34 years. Symptoms were mainly referrable to the chest, with superior vena cava syndrome (SVCO) present in one-third of the patients. Bulky disease was present in over half (58 per cent) and B symptoms were present in 38 per cent of patients. The overall CR rate was 70 per cent and the 5-year OS rates were 56 per cent and 72 per cent for all and CR patients respectively. Five (71 per cent) primary refractory patients and four (66 per cent) relapsed patients died despite salvage therapy. Six relapses occurred at a median of 6 months from treatment. This study showed that primary large B cell lymphoma of the mediastinum is a clinically distinct entity affecting young patients. A significant proportion attained CR and overall, more than half achieved prolonged remission, and most of the relapses occurred early. However, those who failed to attain CR or relapsed still had a poor outcome. An intensive therapy such as autologous bone marrow transplant has to be considered in this subgroup of patients.

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p = 0.001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p = 0.001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p = 0.007). In conclusion, ATRA was shown to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.