The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free survival over 2 years can be achieved in some patients with relapsed lymphoma after high-dose therapy and PBSC transplantation. However, longer follow-up is required to confirm the curability of this approach.

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty- two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty- three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno- occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high- dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.

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Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.

Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation (BMT) from matched unrelated donor (MUD). Currently available HLA-A, -B, and -DR serologic testing may not be sensitive enough to detect clinically relevant donor/recipient (D/R) nonidentity. Better HLA matching of D/R pairs using molecular typing for class II antigens in combination with intensive GVHD prophylaxis may potentially reduce the incidence of GVHD and lead to an improved outcome of MUD transplantation. Between July 1991 and August 1993, thirty consecutive patients with hematologic malignancies underwent MUD transplantation from donors who were identical for HLA -A, -B, and -DR by serologic typing. Twenty-five D/R pairs were matched for DRB and DQB by molecular typing (restriction fragment-length polymorphism and sequence-specific oligonucleotide probe hybridization analyses), whereas five were allele mismatched at either DRB or DQB. All patients also received GVHD prophylaxis with the combination of cyclosporine (CSA), methotrexate (MTX), and prednisone (PSE). The median age was 35 years (range, 15 to 50). The diagnoses were: chronic myelogenous leukemia (CML) in chronic phase (CP) (16), CML in more than CP (3), acute leukemia in more than first complete remission (CR) (8), acute leukemia in first CR (1), and advanced high-grade lymphoma (2). The preparative regimen consisted of 1,320 cGy fractionated total body irradiation (FTBI) and 60 mg/kg cyclophosphamide (CY) daily for 2 days in 17 good-risk patients (CML/CP and acute leukemia first CR); and 1,320 cGy FTBI in combination with 60 mg/kg etoposide and 20 to 60 mg/kg CY in 13 patients with advanced leukemia and lymphoma. All patients received CSA, PSE, and MTX on days 1, 3, 6 for GVHD prophylaxis, and 10 patients also received day +11 MTX. All patients engrafted except one who died early of regimen-related toxicity. The incidence of grade III or IV acute GVHD was 24% (95% confidence interval [CI], 10% to 44%) and that of extensive chronic GVHD was 65% (95% CI, 43% to 84%). At a median follow-up of 13.6 months, 57% of the patients are alive in remission with a median Karnofsky performance status of 90%. The cumulative probability of 2-year disease-free survival for all patients was 53% (95%) CI, 33% to 71%); for good-risk patients, 71% (95% CI, 46% to 87%) and for the poor-risk group, 34% (95% CI, 13% to 64%).(ABSTRACT TRUNCATED AT 400 WORDS)

This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Alkylating agents used either with or without radiation therapy have been associated with the development of myelodysplastic syndrome (MDS) and acute nonlymphoblastic leukemia (ANLL) after treatment of both malignant and nonmalignant disorders. This report describes seven patients with recurrent Hodgkin's disease (HD) evaluated for bone marrow transplantation (BMT) who developed chromosomal abnormalities, and emphasizes the importance of bone marrow cytogenetic studies before bone marrow harvest. Three patients with histologically normal bone marrow underwent autologous BMT and subsequently developed an MDS or ANLL. Four patients had the clonal abnormality detected before bone marrow harvest and did not proceed to BMT.

The human cytomegalovirus (HCMV) a-sequence (a-seq) is located in the joining region between the long (L) and short (S) unique sequences of the virus (L-S junction), and this hypervariable junction has been used to differentiate HCMV strains. The purpose of this study was to investigate whether there are differences among strains of human cytomegalovirus which could be characterized by polymerase chain reaction (PCR) amplification of the a-seq of HCMV DNA and to compare a PCR method of strain differentiation with conventional restriction fragment length polymorphism (RFLP) methodology by using HCMV junction probes. Laboratory strains of HCMV and viral isolates from individuals with HCMV infection were characterized by using both RFLPs and PCR. The PCR assay amplified regions in the major immediate-early gene (IE-1), the 64/65-kDa matrix phosphoprotein (pp65), and the a-seq of the L-S junction region. HCMV laboratory strains Towne, AD169, and Davis were distinguishable, in terms of size of the amplified product, when analyzed by PCR with primers specific for the a-seq but were indistinguishable by using PCR targeted to IE-1 and pp65 sequences. When this technique was applied to a characterization of isolates from individuals with HCMV infection, selected isolates could be readily distinguished. In addition, when the a-seq PCR product was analyzed with restriction enzyme digestion for the presence of specific sequences, these DNA differences were confirmed. PCR analysis across the variable a-seq of HCMV demonstrated differences among strains which were confirmed by RFLP in 38 of 40 isolates analyzed. The most informative restriction enzyme sites in the a-seq for distinguishing HCMV isolates were those of MnlI and BssHII. This indicates that the a-seq of HCMV is heterogeneous among wild strains, and PCR of the a-seq of HCMV is a practical way to characterize differences in strains of HCMV.