Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins

Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.     

Marrow transplantation for non-Hodgkin's lymphoma: a multi-centre study from the European Co-operative Bone Marrow Transplant Group

Twenty-five patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) were treated by allogeneic bone marrow transplantation. For the nine patients transplanted in first complete remission the disease-free survival was 100%; of the nine patients transplanted in subsequent remissions four (44%) achieved long-term disease-free survival but two died of relapsed lymphoma. For the seven patients transplanted at a time when they had active disease, the initial complete remission rate was high but four died of progressive lymphoma and no patient achieved long-term disease-free survival. The incidence of complications associated with allogeneic bone marrow transplantation was similar to that observed in other series of patients transplanted for haematological malignancy and was related to the status of the disease at the time of transplant. Thus allogeneic bone marrow transplantation is a radical but effective treatment for patients with NHL who have 'minimal residual disease'. Efforts to define further the subset of patients who can most successfully be treated by transplantation may improve the overall results.     

Bone marrow transplantation for adult poor prognosis lymphoblastic lymphoma in first complete remission

Twenty-five adult patients, 19 males, six females, age 16-43 years (median 23), with lymphoblastic lymphoma received allogeneic or autologous bone marrow transplantation in first complete remission. Twelve patients were Murphy stage IV with bone marrow and/or CNS involvement and 13 were stage III of whom nine had thoracic involvement. Complete remission was achieved with an intensive anthracycline containing multiagent chemotherapy protocol. Twelve patients with an HLA identical sibling received an allogeneic marrow and 13 without a donor received their own marrow harvested a median of 2 months (0-4 months) after complete remission and purged in vitro with either mafosfamide (eight patients) or anti T-cell monoclonal antibodies and complement (three patients). Bone marrow transplantation was performed 1-7 months (median 3 months) after achieving first complete remission. The conditioning regimen consisted of cyclophosphamide or high dose melphalan and total body irradiation. The actuarial 4-year disease-free survival is 68% (+/- 9% SE). The actuarial probability of relapse was 26% (+/- 3% SE) with a median follow up to 22 months. There was no difference between allogeneic and autologous transplantation with eight out of 12 allo patients in first continuous complete remission 26-45 months after transplant and nine out of 13 auto in continuous complete remission 15-75 months after transplant. These results compare favourably with those achieved with the best chemotherapeutic regimen used for such patients.     

Bone marrow transplantation. Therapeutic usefulness and complications

Eleven patients with a variety of fatal diseases received transplants of allogeneic bone marrow. Transplantation of human leukocyte group A (HL-A) identical marrow to three patients with lymphopenic immunologic deficiency was successful, although one died of a pre-transplant pneumonic process. After transplantation of HL-A nonidentical marrow obtained from his father, one patient with lymphopenic immunologic deficiency died from graft-versus-host disease (GVHD). A patient with chronic mucocutaneous candidiasis had a remission of her disease after bone marrow transplantation with HL-A nonidentical marrow but suffered from chronic diarrhea possibly caused by GVHD. Administration of cyclophosphamide was necessary for the marrow to “take” in patients with functional cellular immunity. One patient had transitory remission of her leukemia after bone marrow transplantation. A patient with grade IVB Hodgkin's disease died, with evidence of bone marrow take and of GVHD despite the fact that donor and recipient were identical at the HL-A locus. Two patients with terminal aplastic anemia died of sepsis shortly after bone marrow transplantation, probably due to a combination of their disease and the administration of cyclophosphamide. HL-A identical marrow failed to take in two patients who had received no preparatory immunosuppressive therapy.     

自体造血干细胞移植对淋巴瘤患者缓解率和生存率的影响

目的:评价自体外周血造血干细胞移植(APBSCT)对提高淋巴瘤患者的缓解率和生存率的作用。方法:回顾性分析53例接受APBSCT淋巴瘤患者临床资料,病理类型以弥漫大B细胞淋巴瘤(DLBCL)为主,占50.94%,中位移植年龄34(12～57)岁,临床分期Ⅲ、Ⅳ期患者占78.8%,年龄矫正的国际预后指数(aaIPI)低危、低中危、中高危、高危患者分别占21.2%、46.7%、15.1%、17.0%。采用统计学分析APBSCT治疗淋巴瘤的疗效及其对生存情况的影响及相关预后影响因素。结果:52例患者成功接受了APBSCT治疗,移植后完全缓解(CR)率65.4%;部分缓解(PR)率19.2%,总反应率(RR)84.6%(CR加PR);其中移植前达CR患者移植后100%CR,PR患者61.2%获CR;1例疾病稳定(SD)患者移植后获CR;17例疾病进展(PD)患者移植后35.3%获CR,17.6%获PR,总反应率为52.9%。中位随访14个月,3年预期总生存(OS)率、无事件生存(EFS)率分别为56%、50%。APBSCT能克服初诊时乳酸脱氢酶(LDH)升高、进展期病变、结外病灶>1、巨块病变、B症状、骨髓浸润所引起的对患者生存期的影响;无法克服体能状态下降、移植前LDH水平升高、进展期病变对生存的影响。结论:APBSCT可提高淋巴瘤患者CR率,改善移植前未达CR患者的OS及EFS,移植前临床特征重新评估对判断预后具有重要意义。     

High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies

Summary Five patients with hematologic malignancies who had relapsed between seven months and eight years after their primary bone marrow transplants were prepared with high dose busulfan/etoposide for second marrow transplanatations from the same donors who had provided the marrow for the primary transplants. The preparatory regimen was well tolerated. All patients engrafted and entered complete remission. Two patients are alive and in continued remission two and ten months after second transplant. One patient died with acute respiratory failure after two months and two patients relapsed again eight and 17 months after second marrow transplantation. The combination busulfan/etoposide may prove to be a suitable preparatory regimen for second bone marrow transplant attempts in selected patients.     

Treatment of isolated central nervous system relapse in high-risk lymphoid malignancy with allogeneic bone marrow transplantation and extended intrathecal therapy

We performed allogeneic bone marrow transplantation (BMT) with an extended period of post-transplant intrathecal (IT) chemotherapy for five patients with acute lymphoblastic leukaemia and non-Hodgkin's lymphoma who had relapsed in the central nervous system either in the very early phase or more than twice. Post-transplant IT was scheduled for a total of 12 doses over 18 months. One patient was found to have subclinical leucoencephalopathy. Disease relapse occurred in one patient and the other patients remained in complete remission for 39-196 months post-BMT. The estimated event-free survival was 80 +/- 17.9% (standard error).     

Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia

Atypical chronic myeloid leukemia (aCML) occurs rarely and is associated with a poor prognosis when treated with conventional chemotherapy. We evaluated the outcome of aCML after allogeneic hematopoietic stem cell transplantation (HSCT). Nine patients were transplanted from HLA-identical siblings (n = 4), HLA-compatible unrelated donors (n = 4) or twin brother (n = 1). Median follow-up was 55 months after transplant (range, 9.1-118.1 months). One patient who was transplanted in advanced disease with bone marrow from his twin brother relapsed 19 months post transplant. This patient was successfully retransplanted from the original donor. All patients remained in complete remission. Analysis of the leukocyte chimerism of peripheral white blood cells and bone marrow buffy coat cells by VNTR-polymerase chain reaction (PCR) and single-nucleotide polymorphism real-time PCR revealed complete chimerism in all patients who had received an allogeneic transplant. One patient suffering from cerebral toxoplasmosis died 9 months post transplant. All other patients were alive at the time of analysis. Our findings suggest that the outcome of allogeneic or syngeneic transplantation in patients with aCML may not be worse than the outcome of transplantation for BCR-ABL-positive CML.     

Treatment results of nine patients with burkitt's lymphoma

Summary From 6/79 until 2/86, 9 patients (median age 39) with Burkitt's lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitt's leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20⁺ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20⁺ months. A second patient is alive at 20⁺ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrom (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.     

Non-myeloablative stem cell transplantation from an HLA identical sibling donor in a case of treatment-related acute myelogenous leukemia

A 50-year-old man was admitted to our hospital because of thrombocytopenia during a follow up study of diffuse large B-cell lymphoma in second complete remission. He was diagnosed as having therapy-related acute myelgenous leukemia (t-AML) on the basis of the bone marrow findings and his chemotherapeutic agent history including alkylating agents. Complete remission was achieved by induction chemotherapy. Although allogeneic stem cell transplantation was thought to be needed, the patient was thought to be ineligible for any myeloablative conditioning regimen because of his age and the history of long term chemoradiotherapy. A non-myeloblative regimen was thus selected. After preconditioning with fludarabine, cyclophosphamide and cytarabine, the patient underwent peripheral blood stem cell transplantation from an HLA identical sibling donor. Complete donor chimeras were obtained on day 28 after transplantation. Regimen related toxicities over grade 2 were not observed. Although he suffered from mild chronic graft-versus-host disease(GVHD), he is in good condition without any signs of relapse during a follow-up period of 33 months. It is suggested that non-myeloablative transplantation is feasible and benefical for patients with t-AML who are often ineligible for myeloablative transplants because of their histories of long term chemoradiotherapies.     

Localized recurrence of acute lymphoblastic leukemia-L3 in the tonsil after 3-years' remission

Recurrence of Burkitt's lymphoma (BL)/acute lymphoblastic leukemia (ALL)-L3 after a long-term remission is very rare. We herein report on a case of BL/ALL-L3 indicating solitary recurrence in the tonsil after a 3-year remission. A 50-year-old man was diagnosed as having Burkitt's type ALL-L3 with involvement of the stomach and abdominal lymph nodes. He was treated with intensive chemotherapy consisting of methotrexate and cyclophosphamide (ALL-BFM86 protocol), and a complete remission was achieved. After sustaining the remission for three years, a swelling of the right tonsil was observed, which was histologically diagnosed as Burkitt's lymphoma. No other organ involvement, including the bone marrow, was observed. The pattern of c-myc rearrangement of the tonsil demonstrated by southern blotting was identical to that of the bone marrow at initial presentation and the recurrence of primary ALL-L3/BL was thus confirmed. The patient was then treated with the ALL-BFM86 protocol and subsequently underwent high-dose chemoradiotherapy with autologous peripheral blood stem cell transplantation (PBSCT). He has now been in complete remission for more than 2 years after his PBSCT.     

Allogeneic bone marrow transplantation in patients with lymphoma relapsing after autologous marrow transplantation

Two patients who underwent autologous bone marrow transplantation for recurrent non-Hodgkin's lymphoma relapsed at 46 and 28 days after the transplant. Both patients had an HLA-identical sibling and were treated with high-dose chemotherapy and allogeneic marrow transplantation. One patient is now 24 months after the allogeneic transplant without evidence of disease. The second patient died on day 7 with interstitial pneumonia. We conclude that high-dose therapy and allogeneic bone marrow transplantation after failure of autologous transplantation for non-Hodgkin's lymphoma is feasible and should be considered in young patients with HLA-identical siblings.     

Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation

Fifty patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) who had relapsed after a complete remission induced by an Adriamycin-containing chemotherapy regimen participated in this prospective pilot study. The patients ranged in age from 16 to 60 years (median 42 years). All patients received dexamethasone, high-dose cytarabine, and cisplatin (DHAP) for two courses at 3- to 4-week intervals. Patients achieving a partial or complete response were scheduled to receive involved-field radiotherapy and high-dose carmustine, etoposide, cytarabine, and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (ABMT). Among 48 evaluable patients (ie, 1 was lost to follow-up and 1 had no measurable disease) 7 patients obtained a complete response (CR) and another 21 patients achieved partial response (PR), whereas the remaining 20 patients failed. One responder died of treatment-related toxicity, and six others declined ABMT. The patient with no measurable disease did not progress on DHAP and was submitted to ABMT. Twenty-two patients underwent ABMT [20 with BEAC and 2 with cyclophosphamide plus total body irradiation (TBI)] of whom 2 (9%) died of toxicity and 10 relapsed. One patient was a suicide at 28 months post-ABMT in CCR and 9 are alive disease-free 24 months to 32 months (median 30 months) post-ABMT. The actuarial 2-year event-free survival for patients undergoing transplantation is 40%. This prospective multicenter trial documents the ability of DHAP followed by ABMT to produce durable complete remission in a significant proportion of patients with relapsed aggressive NHL. Forty-four percent of all patients with relapsed lymphoma who entered the study actually underwent ABMT and 20% of the total group are projected to be long-term disease-free survivors.     

Primary salivary gland lymphoma: a clinicopathologic study of 23 cases in Taiwan

Twenty-three patients with primary salivary gland lymphoma were diagnosed between 1990 and 2001. The sites of involvement were the parotid gland in 13, the submandibular gland in 9 and the minor salivary gland in 1. The sites of lymphoma involvement beyond the salivary glands were the cervical lymph nodes in 7, bone marrow in 3, the axillary lymph nodes in 3, the nasopharynx in 2, the abdominal lymph nodes in 2, the palate, the subconjunctiva, and the spleen in 1 each patient. Histologically, 19 patients had lymphomas of mucosa-associated lymphoid tissue (MALT) with myoepithelial sialadenitis in 13, 3 patients had diffuse large cell lymphomas and 1 had follicular lymphoma. Six patients were in stage I, 4 in II, 1 in III and 12 in IV. Eight of 23 patients (35%) had autoimmune diseases before or after the diagnosis of NHL and all suffered from MALT lymphoma. Four patients with parotid MALT lymphoma had primary or secondary Sjogren's syndrome. One each patient suffered from hyperthyroidism, systemic lupus erythematosus, membranoproliferative glomerulonephritis and cryoglobulinemia, respectively. All the 6 stage I patients had achieved complete remission (CR) without relapses 17-84 months (median 44 months) after treatment. Excluding a stage IV patient with follicular lymphoma who died at 3.5 months without treatment, CR was achieved in all of the remaining 16 patients. However, a high relapse rate (9/16, 56%) was noted in stage II-IV patients. These patients tended to relapse in the original sites, but achieved CR again after chemotherapy or radiotherapy. One patient with MALT lymphoma developed histologic transformation into diffuse large lymphoma during relapse and died of refractory disease. Overall, only 2 patients succumbed. The overall survival and relapse-free survival rates at 5 years were 94.7 and 51.4%, respectively. Thus, salivary gland lymphoma proved to be an indolent disease.     

Involved field radiation, fractionated total body irradiation, high dose cyclophosphamide, and autologous bone marrow transplantation in the treatment of malignant lymphomas

We report the results of intensive therapy and autologous bone marrow transplantation (BMT) in 23 patients with malignant lymphoma (eight Hodgkin's disease and 15 non-Hodgkin's lymphoma) who failed primary therapy. All patients had evidence of disease prior to transplant therapy: 10 had never achieved a complete remission and 13 were in relapse. The preparative regimen included involved field radiation followed by fractionated total body irradiation and high dose cyclophosphamide. A complete remission was achieved in 15 patients, 11 of whom continue in unmaintained complete remission from 27 to 72 months after BMT (median follow-up of 52 months). Of the remaining patients, five did not achieve a complete remission and three died of early toxicity. The event-free survival of the entire group is 47%. Disease status at the time of BMT was significantly correlated with patient outcome. The event-free survival of 13 patients in whom there was no objective evidence of tumor growth on conventional dose therapy was 77% compared with only 10% in patients with tumors progressing on conventional dose therapy (p less than 0.002). All six patients transplanted in untreated relapse continue in unmaintained remission, suggesting that debulking chemotherapy may not be necessary before BMT. Alternative approaches are needed in patients whose tumors progress on conventional dose therapy.     

Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation

The prognosis for blastic natural killer (NK) cell lymphoma is generally dismal. We report a patient who was successfully treated with unrelated cord blood transplantation (UCBT). A 15-year-old boy was diagnosed as having blastic NK cell lymphoma in the cervical lymph nodes. Autologous peripheral blood stem cell transplantation was performed on achieving a complete remission. However, the disease recurred in the bone marrow 6 months later. Chemotherapy induced a second remission and the patient received UCBT with a conditioning regimen consisting of total body irradiation, thiotepa and cyclophosphamide. Chronic GVHD of the lung occurred, but it was well controlled with steroids. At the time of writing, he remains in remission 18 months after UCBT with an excellent performance status. UCBT may be an option for patients with blastic NK cell lymphoma.     

Bone marrow transplantation for non-Hodgkin's lymphoma in children and young adults. A pilot study

Allogeneic bone marrow transplantation was performed in 10 patients with disseminated Burkitt's lymphoma or poor-prognosis T-cell lymphoblastic lymphoma. All patients received a cytoreduction regimen consisting of cyclophosphamide, cytosine arabinoside, bis-chloro-nitroso-urea, and total-body irradiation. Eight patients received marrow from HLA-matched sibling donors. One patient received marrow from a parent donor and one patient died during initial cytoreduction and did not undergo total-body irradiation or marrow infusion. Six patients had Burkitt's lymphoma stages III and IV at diagnosis, and three of the six are alive at 18, 28, and 73 months. Four patients had T-cell lymphoblastic lymphoma, stages III and IV at diagnosis, and two of the four are alive at 29 and 49 months. Overall survival in the nine patients who underwent transplantation is 56 percent by life-table analysis. Follow up for the surviving patients ranges from 18 to 73 months (median 29 months). All five survivors are at home with unmaintained remissions.     

Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor

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.     

Successful treatment of extramedullary blast crisis of chronic myelogenous leukemia with imatinib mesylate (STI571)

We describe a patient with chronic myelogenous leukemia (CML) who developed extramedullary blast crisis, and was successfully treated with imatinib mesylate (STI571). A 42-year-old man had been diagnosed with chronic phase Philadelphia chromosome (Ph)-positive CML and treated with interferon-alpha. He achieved partial cytogenetic response. Two years after the diagnosis, he presented with superficial lymphadenopathy in his neck and supraclavicular regions. Lymph node biopsy disclosed the infiltration of myeloblasts. Although the patient's bone marrow was without increasing blasts at that time, cytogenetic response was no longer observed. STI571 at a dose of 600 mg/day was initiated, and led to the complete disappearance of lymphadenopathy within a month and also to major cytogenetic response in the bone marrow (90% Ph-negative metaphases). Subsequently, the patient underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor and was in complete remission without evidence of extramedullary disease 12 months after transplantation.     

Allogeneic marrow transplantation in non-Hodgkin's lymphoma

Nine individuals between 15 and 43 years of age with non-Hodgkin's lymphoma underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. These individuals were not considered optimal candidates for autologous transplantation chiefly because of marrow involvement or resistance to chemotherapy. All patients engrafted and eight achieved complete remission. Three patients relapsed; one patient died of transplant-related complications. Five individuals are disease-free survivors between 103 and 1169 days following transplantation. Of three individuals with relapsed Burkitt's lymphoma none experienced a sustained disease-free interval following transplantation. Three of four individuals with large cell or lymphoblastic lymphoma are surviving 585 to 1169 days following transplantation. Allogeneic marrow transplantation following busulfan and cyclophosphamide appears reasonably safe and is effective in selected patients with non-Hodgkin's lymphoma who are not good candidates for autologous marrow transplantation.