High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy.

PURPOSE: High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients. PATIENTS AND METHODS: Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program. RESULTS: Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation. CONCLUSION: Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.     

抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

 目的　探讨抗CD20单克隆抗体（利妥昔单抗,商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法　21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解（CR）,难治性病例为16例,包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375 mg／m2。结果　移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存。21例患者中位随访24（1～68）个月,复发、死亡4例（19 %）,其余17例均无病生存,2年无病生存（EFS）和总生存（OS）率均为81.0 %。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论　APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。     

High-dose Thiotepa,Busulfan, Cyclophosphamide,and Autologous Stem Cell Transplantation as Upfront Consolidation for Systemic Non-Hodgkin Lymphoma With Synchronous Central Nervous System Involvement

IntroductionSynchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach.Patients and MethodsWe conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions.ResultsTwenty patients were identified through the transplant database. The median age at diagnosis was 53 years (range, 37-65 years). The majority had diffuse large B-cell lymphoma histology (n = 17; 85%). The sites of CNS involvement were parenchymal (n = 12; 60%) and leptomeningeal disease (n = 9; 45%). All patients received systemic and CNS-directed therapy prior to transplant, with the most common approaches being R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) (n = 13; 65%) and high-dose intravenous methotrexate (n = 16; 80%), respectively. With a median follow up of 4.4 years after ASCT (range, 2 months-8.5 years), the Kaplan-Meier estimates of 4-year progression-free and overall survival were 77% (95% confidence interval, 48%-91%) and 82% (95% confidence interval, 54%-94%), respectively.ConclusionCNS-directed high-dose chemotherapy and ASCT provides durable remission for patients with synchronous aggressive lymphoma and should be strongly considered as consolidative therapy for eligible patients with systemic NHL with CNS involvement in first complete remission.     

High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23 - 147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age > 35 years (P = 0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P = 0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.     

Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant

Dose-intensive chemotherapy with autologous stem cell support is commonly used in resistant/refractory cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the role of tandem transplantation in these patients. We used non cross-resistant conditioning regimens with thiotepa, mitoxantrone and carboplatin (TMJ) followed by ifosphamide, carboplatin and etoposide (ICE) with autologous stem cell rescue in an attempt to maximize dose intensity and achieve long-term remission. Seventy-six patients were included in this study. Twenty-nine patients with HD and 47 with NHL underwent autologous stem cell transplant using TMJ as the conditioning regimen for the first transplant. Of these, 49 patients proceeded to the second transplant using ICE as the conditioning regimen. In 57 patients, only peripheral blood cells were used and in 11 patients both bone marrow and peripheral stem cells were used. Twelve patients died due to treatment-related toxicity. On an intent to treat basis, 32.14% of patients with HD refractory to initial or subsequent therapy survived long term as opposed to 12.76% of patients with NHL. With a median follow-up of 83 months (range 25 - 110 months), the median disease-free survival of patients with HD was 7 months, as opposed to 2 months for patients with NHL. Multivariate analysis identified that patients with HD had a superior outcome if they were less than 35 years of age and did not have B symptoms. Dose-intensive chemotherapy with tandem transplantation is an option in patients with resistant/refractory lymphoma who have very limited treatment options and poor prognosis.     

Treatment of primary CNS lymphoma (PCNSL) following successful treatment of systemic non-Hodgkin’s lymphoma (NHL): a case series

Management of PCNSL occurring after successful treatment of systemic non-Hodgkin’s lymphoma (NHL) is poorly defined. Illustrate a treatment approach for PCNSL following prior treatment of a systemic NHL. A retrospective case series of 6 patients (mean age 60 years; range 46–65) diagnosed with a diffuse large B cell lymphoma of the CNS following prior successful treatment of a systemic NHL (low-grade in 2; high-grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7–18). In 4/6 patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab (immunochemotherapy) followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (ASCT) with total body irradiation (TBI) and multi-agent conditioning chemotherapy (BEAM: carmustine, etoposide, cytarabine, melphalan). 5/6 patients had a radiographic complete response to immunochemotherapy and were treated with ASCT. 4/5 patients were free of disease following ASCT with a mean follow-up of 3 years (range 0.5–4 years). There were no toxic deaths and all patients transplanted successfully engrafted within 28 days (mean 18). Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by ASCT) for PCNSL occurring metachronously after successful treatment of systemic NHL appears safe and effective.     

Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy

We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.     

Potential drug interaction with paclitaxel and highly active antiretroviral therapy in two patients with AIDS-associated Kaposi sarcoma

Highly active antiretroviral therapy (HAART) consisting of multiple combinations of antiretroviral agents that inhibit HIV (HIV) replication has been associated with improvements in CD4+ T-lymphocyte cell counts, suppression of HIV replication, and regression of HIV-associated Kaposi's sarcoma (KS). Several of these agents have complex drug-drug interactions and have the potential to aggravate paclitaxel-associated toxicities. Herein two patients with KS are described who received paclitaxel while on HAART and who developed life-threatening toxicities. These cases are presented to alert clinicians to potentially serious drug interactions that can occur between various components of HAART and paclitaxel. Clinicians contemplating taxane-based chemotherapy for HIV-associated KS should carefully monitor patients for adverse events and, depending on their patient's HAART regimen, consider reducing the taxane dose.     

The changing face of HIV‐associated lymphoma: what can we learn about optimal therapy inl the post highly active antiretroviral therapy era?

Epidemiological data indicate that the risk of developing non-Hodgkin lymphoma (NHL) in HIV positive individuals is related to age and CD4 count (i.e. degree of immunosuppression). The prognosis of patients with HIV-NHL has been shown to be linked to several features including age, stage, modified IPI, prior AIDS diagnosis, CD4 count, immunoblastic pathology, LDH, and HAART use. These features are, as would be expected, a mixture of prognostic factors relating to both the HIV, and to the NHL. Population studies indicate that the incidence of associated (HIV-NHL) may be reducing with the advent of HAART, although not all studies concur. However, most population-based studies have not as yet shown a significant improvement in the survival of patients with HIV-NHL with HAART. The optimal chemotherapy for these patients is unknown, although it is generally accepted that CNS prophylaxis is mandatory. There is currently no good evidence of any survival benefit with increased dose intensity from large RCT. However, it must be borne in mind that the large randomised studies comparing differing dose intensities were undertaken before the advent of effective HAART. There is some evidence that there may be a subset of good prognosis patients who may benefit from more intensive therapy. Given that the prognosis of patients with HIV can now be considerably improved with HAART, we cannot necessarily assume that the same results would apply with regard to chemotherapy dose intensity. There is some evidence that there is a survival benefit from the addition of HAART to chemotherapy, although this is retrospective. It is likely, however, that the reason for this is that the HAART improves the prognosis of the patients from their HIV, and therefore reduces the number of patients dying from other HIV-related illnesses whilst in remission from their lymphoma, as was seen in large numbers of patients in the earlier chemotherapy trials. It must not be forgotten that the prognosis of the patient's NHL is intimately linked to their prognosis with respect to the HIV. Although the number of patients with HIV-NHL is currently few, there is a need for more trials of chemotherapy, particularly now in the HAART era, when the prognosis from the point of view of the HIV has improved so much. In particular, the issue of dose intensity needs revisiting for patients whose overall prognosis can be improved by commencing HAART. Patients with HIV-NHL should be managed at specialist centres, and where possible should be managed as part of RCT.     

Successful treatment of aggressive HIV-associated non-Hodgkin's lymphoma with combination chemotherapy,biotherapy with rituximab and HAART: presentation of a therapeutic option

The incidence of non-Hodgkin's lymphoma (NHL) in individuals infected with human immunodeficiency virus (HIV) is more than 60 times higher than in matched controls. In the vast majority of cases aggressive pathological subtypes and advanced stages prevail, extranodal sites are involved and systemic symptoms are present. The prognosis of HIV-NHL remains poor and the optimal therapeutic approach has yet to be defined. We report a 48-year-old Ethiopian woman with advanced-stage HIV infection, who developed diffuse large cell, immunoblastic type B-cell NHL and was treated with a modified CHOP-like chemotherapy combined with Rituximab and supported with growth factor. Highly active antiretroviral therapy (HAART) and opportunistic infections prophylaxis were administered concomitantly. The patient completed 6 cycles of therapy and currently, 76 weeks after diagnosis, is in complete clinical remission. Despite the fact that there was a transient decrease in the CD4-positive cell number and a 1.5 log increase in plasma viral load there were no opportunistic infections, nor was life-threatening toxicity seen. Rituximab seems a well-tolerable and advantageous adjunct to chemotherapy and HAART in the treatment of aggressive HIV-associated NHL andshould be investigated in large trials in the future.     

利妥昔单抗联合高剂量治疗和自体外周血干细胞移植治疗侵袭性B细胞淋巴瘤的多中心前瞻性研究

目的 探讨在高剂量治疗联合自体外周血干细胞移植的基础上,加用利妥昔单抗治疗侵袭性B细胞淋巴瘤的可行性和疗效.方法 12个癌症研究中心共入组28例侵袭性B细胞淋巴瘤患者,其中22例为新诊断患者,6例为复发患者.每例患者共接受4次利妥昔单抗静脉输注,即在外周血干细胞动员化疗的前1天、动员化疗的第7天、干细胞回输的前1天和回输后的第8天各给予1次,每次375 mg/m2,共1500 mg/m2结果 高剂量治疗后,所有患者均达到完全缓解.中位随访37个月时,全组患者的4年总生存率和无进展生存率分别为75.0%和70.3%,新诊断患者的4年总生存率和无进展生存率均为72.7%.全组患者对利妥昔单抗治疗的耐受性较好,不良反应多为1、2度.结论 在高剂量治疗联合自体造血干细胞移植的基础上加入利妥昔单抗治疗侵袭性B细胞淋巴瘤是可行的,并且可能使患者的生存获益.     

Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study.

PURPOSE: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). RESULTS: Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). CONCLUSION: PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.     

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.     

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically.     

The impact of pre- and post-transplantation positron emission tomography using 18-fluorodeoxyglucose on poor-prognosis lymphoma patients undergoing autologous stem cell transplantation

BACKGROUND: In patients with lymphoma who had a poor prognosis, pretransplantation 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) was important for the evaluation of response and outcome. However, little is known about the correlation of FDG-PET with post-transplantation PET. The current study was designed to ascertain whether positive pretransplantation PET images are modified by the conditioning regimen. METHODS: Sixty consecutive patients who had achieved remission and underwent consolidation by autologous stem cell transplantation (ASCT) had PET images obtained before ASCT (after 3 or 4 chemotherapy cycles) and 100 days after ASCT. The correlation was explored between the presence of abnormal 18-FDG uptake (PET positive) or its absence (PET negative) and patient outcomes. RESULTS: Before ASCT, 31 patients achieved complete remission (CR), and 23 patients achieved uncertain CR. Before ASCT, 44 patients (75%) were had negative PET images; and, after ASCT, 48 patients (80%) had negative PET images. One year after ASCT, the estimated event-free survival (EFS) rate was 80% in patients who had negative pre-ASCT PET images compared with 43% in patients who had positive pre-ASCT PET images (P = .0002). The EFS rate was 81% in patients who had negative post-ASCT PET images compared with 25% in patients who had negative post-ASCT PET images (P < .0001). In multivariate analysis, only the results for pre- and post-ASCT PET images retained prognostic value, with relative risks of failure estimated at 4.9 and 11.9, respectively. CONCLUSIONS: A positive pre-ASCT PET image indicated a high risk of ASCT failure, which was increased by a positive post-ASCT PET image. For patients with lymphoma who have positive pre-ASCT PET images, more investigations using new treatment approaches will be required. For patients who have negative pre-ASCT PET images, obtaining post-ASCT PET images does not seem to be mandatory.     

AIDS malignancies in the era of highly active antiretroviral therapy

The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which will conclude in the May 2002 issue, analyzes the impact of HAARTon the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.     

Autologous bone marrow transplantation in relapses of chemotherapy-sensitive aggressive non-Hodgkin's lymphoma: long-term outcome

Eleven patients with relapsed intermediate to high grade non-Hodgkin's lymphoma (NHL) responding to induction treatment were treated with high-dose chemotherapy (CBV or ICBV conditioning regimen) plus autologous bone marrow transplantation as early consolidation treatment. At 6 years, relapse-free survival is 27.3% and overall survival is 36.4%. Patients with bone marrow involvement from NHL before the induction therapy did not have a worse prognosis. Despite the long-term follow-up, no secondary myelodysplasia or acute leukemia occurred in our patients. Within the limitations of patient number and selection, our retrospective study confirms the importance of tumor responsiveness and long-term follow-up. Patients with relapsed, but chemotherapy-sensitive NHL can achieve prolonged survival after high-dose chemotherapy plus autologous bone marrow transplantation.     

A Review of Autologous Stem Cell Transplantation in Lymphoma

Purpose of Review

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients.

Recent Findings

There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL.

Summary

Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

     

Autologous Stem-Cell Transplantation for Poor-Risk and Relapsed Intermediate- and High-Grade Non-Hodgkin's Lymphoma

The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5–69 years). The median number of prior chemotherapy regimens was 2 (range, 1–4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3–158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1–12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%–61%), 47% (95% CI: 40%–53%), and 47% (95% CI: 40%–54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%–81%) as compared to 30% (95% CI: 16%– 45%) for induction failure and 34% (95% CI: 26%–42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.