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PubMed2004

[The treatment of lung cancer relapse after the lung resection].

UNLABELLED: The aim of the study was to analyze the patients with the relapse of tumors after lung resection. MATERIAL AND METHODS: One hundred eight patients with lung cancer were operated at Lithuanian Institute of Oncology during period of 1992-2002. To 28 patients pneumonectomy was performed, 4 - bilobectomy, 51 - lobectomy, 23 - wedge resection, 2 - segmentectomy. According to the stage of tumor operations more often were performed in III stage of the disease - to 62 patients, in II - 20, in I - 12 and in the IV - 14. The most common histologic type of tumor was squamous cell carcinoma - 57 patients, adenocarcinoma - 29, small cell carcinoma - 12, anaplastic carcinoma - 4, other types of tumor were rare. The stage of disease had influence upon the time for the relapse of tumor. The dissemination of tumor was detected in 9 patients with II ir III stage of disease. The treatment of the relapse of lung tumor was the following was: 31 patients received radiotherapy, 4 - photodynamic therapy, 12 - radiotherapy with chemotherapy, 20 - chemotherapy. RESULTS: According to the data of March 31, 2003, 98 patients died from carcinoma, 10 patients lived with the signs of disease. Median survival after relapse of tumor was better in patients with I stage of disease - 26.2 months, II - 20.7 months, III - 13.9 months, IV - 8.2 months. CONCLUSIONS: In the case of locally extended tumor with metastases in regional lymph nodes after lung resection the relapse of tumor was most common. The treatment of the relapse of tumor in early stages of disease was most effective.

Adenocarcinoma↗

PubMed1992

Cognitive behavior therapy and relapse of nonbipolar depression: parallels with pharmacotherapy.

The risk of relapse was studied in 44 major depressives following successful acute treatment with cognitive behavior therapy (CBT). Patients entered a 1-year prospective followup with independent clinical assessments at 1, 3, 6, 9, and 12 months. Of these patients, 15 (34%) relapsed; correlates included marital status, recurrent subtype, higher initial and residual ratings of depressive severity, and slower response to therapy. Both married status (p = .008) and fully recovered status (p = .02) were significantly and independently related to decreased risk of relapse using the Cox proportional hazard method. These findings provide further documentation of a relationship between residual symptomatology and relapse after cessation of active treatment and closely parallel findings pertaining to risk of relapse after acute antidepressant pharmacotherapy of unipolar depression. As in pharmacotherapy, a longer period of continuation treatment may be indicated for patients at risk for relapse after an initial course of time-limited therapy with CBT.

Adult↗

PubMed2005

In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

Adolescent↗

PubMed1992

[Second marrow transplantation following high dose busulfan, etoposide, and Ara-C after testicular relapse in a patient with AML].

Prognosis of second marrow transplantation after leukemia relapse is usually gloomy. We report a patient with AML who was successfully treated by the second marrow transplant following high dose busulfan, etoposide, and Ara-C for the testicular relapse after the first marrow transplantation. A 24-year-old man was diagnosed as having acute myeloid leukemia (AML) in September, 1988. In December of 1989 when he was in early relapse after his 2nd remission, he received the first allogeneic BMT from his HLA identical brother after high dose busulfan and cyclophosphamide conditioning. His posttransplant course was uneventful and graft versus host disease was not observed. Three months after BMT, he noticed swelling on right testicle. Leukemic cell infiltration was confirmed by aspiration cytology. The testicular relapse was followed by marrow relapse. After successful remission induction chemotherapy, he received 17.5 Gy testicular irradiation and second marrow transplantation using high dose busulfan, etoposide, and Ara-C conditioning. Although his posttransplant period was complicated by severe mucositis, high fever and bronchopneumonia, hematologic recovery was obtained by 3 weeks after the second transplant. He is now continuing in complete remission 18 months after the second BMT. This case report suggests that the combination of high dose busulfan, etoposide, and Ara-C could be a choice as a conditioning regimen for resistant AML relapsing after BMT.

Adult↗

PubMed2005

[Treatment effect of DICE regimen on patients with relapsed or refractory intermediate and high grade non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: So far, there is still no standard salvage regimen for relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rates (RR) of NHL patients received common salvage regimens, such as DICE, ESHAP, MINE, and EPOCH, are only 30%-70%. This study was to evaluate the efficacy and safety of DICE regimen, as a salvage regimen, in treating patients with relapsed or refractory intermediate and high grade NHL. METHODS: Thirty-five patients with relapsed or refractory intermediate and high grade NHL, who had been pretreated with chemotherapy dominated by CHOP or CHOP-like regimen with a median of 6 cycles (ranged 2-12 cycles), were salvaged by DICE regimen from Jun. 1999 to Jan. 2004. Of the 35 patients, 14 were T-cell original, and 21 were B-cell original. RESULTS: The 35 patients received DICE regimen with a median of 4 cycles (ranged 2-7 cycles). All patients were assessable in the efficacy and adverse events. The total RR was 74.3% with complete response (CR) rate of 31.4%, median response time (MST) of 4 months (ranged 1-30 months), median time to failure (TTF) of 7 months (ranged 2-34 months),median survival time (MST) of 14 months (ranged 3-51 months), and 2-year survival rate of 33.3%. The RRs of T-cell and B-cell NHL were 85.7% and 66.7%. The CR rate was higher in T-cells NHL than in B-cell NHL (50.0% vs. 19.0%, P=0.073). Elevated serum lactate dehydrogenase (LDH) and bulky disease were high risk factors of the efficacy of DICE regimen (P < 0.05). The response to DICE reginmen was an independent prognostic factor of patients with relapsed or refractory NHL (P = 0.001). The major toxicity was myelosuppression. Incidences of neutropenia and thrombocytopenia of grade III-IV were 71.4% and 8.6%. CONCLUSIONS: DICE regimen is a safe and effective salvage regimen for the patients with relapsed or refractory intermediate and high grade advanced NHL. Elevated serum LDH and bulky disease are the adverse prognostic factors. The response to DICE regimen may directly influence survival time of patients with relapsed or refractory NHL.

Adolescent↗

PubMed2005

Influence of treatment and immunological recovery on tuberculosis relapses in HIV-infected patients.

SETTING: Studies on tuberculosis (TB) relapse in HIV-infected patients show contradictory results regarding the optimal duration of treatment. OBJECTIVE: To assess the incidence of TB relapse and associated factors in HIV-infected patients receiving a 9-month tuberculostatic regimen and concomitant HAART. PATIENTS AND METHODS: Observational prospective study recording 156 episodes of TB in 137 patients, most of whom were on a 9-month regimen of daily isoniazid and rifampicin-based TB treatment. The primary outcome measure was relapse after completion of therapy. RESULTS: Forty episodes were excluded due to death or loss to follow-up. The median follow-up was 24 months. Twenty-seven episodes of TB relapse were observed in 22 patients, yielding a relapse rate of 1.9/100 patient-years in those on a regimen of > or = 9 months. A high recurrence rate was observed in those who had prematurely suspended treatment. Treatment duration > or = 9 months and achieving both an undetectable viral load and increasing CD4-cell counts with HAART were associated with the absence of TB relapses. CONCLUSIONS: Considering its safety and tolerance, our results suggest that a 9-month regimen would be recommendable in patients with severe immunosuppression until the optimal duration of TB treatment in HIV-infected patients has been defined in a randomised clinical trial including HAART.

Adult↗

PubMed2006

Promoting repeat tobacco dependence treatment: are relapsed smokers interested?

BACKGROUND: Promotion of repeat tobacco dependence treatment among relapsed smokers interested in "recycling" (repeat quit attempt) may be a promising approach to increase quit rates. OBJECTIVE: To report relapsed smokers' interest in recycling and their treatment preferences. STUDY DESIGN: Descriptive analysis of a population of relapsed smokers who were randomized to receive a recycling intervention strategy to increase tobacco dependence treatment rates, as part of a randomized controlled trial at 5 Veterans Affairs medical centers. METHODS: Individuals prescribed a tobacco dependence medication in 2002 were eligible and were identified from the Department of Veterans Affairs Pharmacy Benefits Management database. Intervention group participants (n = 951) were contacted for a standardized telephone interview approximately 6 months after the prescription fill date to assess smoking status, interest in recycling, and treatment preferences. Bivariate analyses and generalized linear mixed-model regressions were used to describe outcomes. RESULTS: The response rate to the intervention telephone call was 62% (586/951), at which 61% (357/586) of respondents had relapsed. Almost two thirds of relapsed smokers were interested in recycling within 30 days. Of these, 91% wanted behavioral or pharmacologic smoking cessation treatment, and 64% wanted behavioral and pharmacologic treatment. In multivariate analyses, independent predictors of interest in recycling within 30 days included black race, lower smoking level, and greater number of smoking-related medical conditions. CONCLUSION: Most smokers who attempt to quit but relapse want to quit again right away, and most are interested in receiving behavioral and pharmacologic treatment.

Adult↗

PubMedDate not supplied

[Relapses in children with nephroblastoma--a single centre experience].

UNLABELLED: The aim of the study was to assess the incidence of relapse and outcome of treatment in children with nephroblastoma relapse. MATERIAL AND METHODS: In the years 1989-2002 at our centre 67 children were treated for nephroblastoma. Patients were divided into two subgroups. Group I comprised 25 children treated in accordance with the SIOP-9 programme, whilst group II consisted of 42 patients following the SIOP 93-01 protocol. RESULTS: In group I, five children had relapse diagnosed: local in 2, pulmonary in 2 and cerebral in one case. Two of the cases were diagnosed during the treatment, and the other 3 after 1 to 19 months from the completion of treatment. In group II relapse was diagnosed in 4 children: local in 2 and pulmonary in 2 cases. One case was diagnosed while on treatment, and the other 3 were diagnosed 1,2 and 4 months after completion of treatment. Among the children who followed the SIOP-9 programme three patients died, while among those following SIOP 93-01 two patients died. CONCLUSIONS: The prognosis in patients who relapsed remains uncertain. The histological type of tumour and the moment of relapse occurrence are significant prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis.

Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis.

Animals↗

PubMed1991

Outcome of treatment of first relapse of Hodgkin's disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988.

The outcome of treatment for a first relapse of Hodgkin's disease after primary chemotherapy was analyzed in 80 patients. They were divided into four groups: group 1 (n = 24) had initially been treated with three cycles of (mechlorethamine, vincristine, prednisone, and procarbazine [MOPP]) and wide-field irradiation therapy; group 2 (n = 25) had six cycles of MOPP; group 3 (n = 15) and group 4 (n = 16) both initially received MOPP/ABVD (MOPP plus doxorubicin, bleomycin, vinblastine, and dacarbazine) or MOPP/ABV hybrid, but group 3 received conventional salvage regimens whereas group 4 was treated with high-dose chemotherapy and autologous bone marrow transplantation as salvage therapy (n = 16). Freedom from second failure (FF2F) was used as the major endpoint. Actuarial FF2F for all patients was 38% after a median follow-up of 75 months for patients who were alive. Risk factor analysis was performed on the 71 patients who had been treated with curative intent. The presence or absence of any one of three risk factors had a strong negative impact on outcome: stage IV disease at primary diagnosis, B symptoms at relapse, or a time from primary treatment to relapse of less than 1 year. Actuarial FF2F at 5 years was 17% in the group of patients with one or more of these three factors present (n = 49). If none of these factors was present, FF2F was 82% (n = 22) (P less than .001). Even high-dose chemotherapy and autologous bone marrow transplantation were not able to overcome the negative impact of one or more risk factors (FF2F = 19%, n = 12). The outcome of salvage treatments depends most on the presence or absence of these three risk factors and less on the type of salvage treatment. Patients with none of these risk factors present have an excellent outcome if they are treated with non-cross-resistant chemotherapy, or radiotherapy, or both. Novel approaches are needed for patients with one or more of these factors present. Reports on salvage treatments for Hodgkin's disease in first relapse after primary chemotherapy should include data on the proportion of patients having stage IV disease at diagnosis, B symptoms at relapse, and a time from primary treatment to relapse of less than 1 year.

Adolescent↗

PubMed1991

Successful treatment of paralytic relapses in adoptive experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance.

We have previously demonstrated that Ag-specific tolerance induced by the i.v. administration of splenocytes coupled with neuroantigens, such as mouse spinal cord homogenate, myelin basic protein (MBP), and proteolipid protein, and their encephalitogenic peptides, results in dramatic inhibition of clinical and histologic signs of both actively induced and adoptively transferred relapsing experimental autoimmune encephalomyelitis (R-EAE). We report here that the administration of splenocytes coupled with mouse spinal cord homogenate (i.e., a mixture of neuroantigens), after the first paralytic episode of adoptive R-EAE triggered by MBP-specific T cells but before the appearance of the first relapse, effectively reduced the onset and severity of all subsequent relapses, as determined by both clinical and pathologic criteria. In contrast, the i.v. administration of splenocytes coupled with MBP (i.e., the specificity of the initiating T cell response), under similar conditions, effectively inhibited the initial clinical relapse, but subsequent relapses occurred with the same incidence rate and severity as those in control animals. Collectively, these results demonstrate that neuroantigen-specific tolerance is effective at specifically down-regulating an ongoing autoimmune response. This may have potential clinical applicability for treatment of autoimmune diseases. The results also support the hypothesis that the neuroantigen specificity of later relapses of R-EAE may be due to effector T cells with specificities different from those that triggered the initial clinical episode. Thus, potential therapy for the advanced stages of R-EAE, and perhaps other autoimmune diseases, may have to be directed not simply against the effector cells initiating the disease but also against effector cells with differing specificities recruited as a result of tissue damage occurring in the initial acute disease.

Animals↗

PubMed2006

Pattern of relapses in Iranian patients with ulcerative colitis. A prospective study.

BACKGROUND: The pattern of relapses in patients with ulcerative colitis (UC) has a significant role in taking decisions about the therapy and the follow up of patients. This study is designed to find out the pattern, time and severity of relapses in Iranian patients with UC. METHOD: From 1991 to 2003, a period of 13 years, the pattern of relapses in 163 patients with UC who had been admitted to a private referral gastroenterology clinic in Iran were evaluated. RESULTS: 163 patients (58.3% female, 41.7% male) were included, aged from 17 to 74 years with mean age of 38.9 ± 12.3 years. Mean follow up time was 52.7 ± 41.4 months (ranges 12 and 155 months). Mean relapse chance was 0.028 ± 0.036 for each patient in every month (ranges 0-0.21). The mean time from the initial attack to the first relapse was 23.8 ± 22.5 months, which was not the same in patients with different primary disease severity (p = 0.03). CONCLUSION: The time and severity of the relapses relate to the severity of UC. Iranian patients have a milder course of the disease.

Adolescent↗

PubMed1992

Combination chemotherapy MOCCA in resistant and relapsing multiple myeloma. Finnish Leukaemia Group.

80 patients with resistant or relapsing multiple myeloma received a combination of vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA) as a second-line chemotherapy. 27 of them were resistant to primary chemotherapy with alkylating agents, and 53 had relapsed after initially responding to these drugs. An objective response was achieved in 39 patients (49%): in 14 patients who were primarily resistant (52%) and in 25 patients who had a relapse (47%). Of 41 patients relapsing during maintenance chemotherapy 14 (34%) responded, while 11 of 12 patients (92%) treated for a relapse off-therapy responded. The median duration of response was 22 months. Severe complications, in most cases infections, occurred in 30% of patients, and were fatal in 9% of the cases. According to our experience the five-drug combination MOCCA is an effective second-line chemotherapy for myeloma patients primarily resistant to or relapsing after therapy with single alkylating agents.

Aged↗

PubMed1991

In vitro chemosensitivity of lymphoblasts at relapse in childhood leukemia using the MTT assay.

Lymphoblasts from 21 previously untreated patients with acute lymphoblastic leukemia (ALL) and 31 patients in relapse were tested for chemosensitivity. Blast cells were cultured with 22 anticancer drugs for 4 days and assayed by MTT dye using a scanning microplate photometer. The percent cytotoxicity index (%CI) and LD50 (micrograms/ml) were calculated for each drug. The mean absorbances (+/- S.D.) of 1 x 10(5) cells in the untreated group and relapsed groups in control wells were 0.219 (+/- 0.126) and 0.385 (+/- 0.147), respectively (p less than 0.01). Cells in the untreated group were more sensitive in vitro to vincristine, prednisolone, L-asparaginase (L-ASP), vinblastine, 5-fluorouracil, epirubicin, bleomycin (BLM), and etoposide (VP16) with respect to the %CI value and to L-ASP, VP16, BLM, and mitoxantrone with respect to the LD50 value than those in the relapsed groups. In contrast, no significant differences were observed for the other 13 drugs. There was also a significant difference in sensitivity within the relapsed group--13 having good clinical response and 15 showing no response to chemotherapy--with regard to four drugs, mitomycin C, neocarzinostatin, L-ASP, and teniposide. Cells in the relapsed group had more heterogeneous chemosensitivity than those in the untreated group, and divided into sensitive and resistant types, but large interindividual differences existed. The MTT assay and LD50-drug resistance percentile curves are useful for the selection of effective drugs in both untreated and relapsed patients with acute leukemia.

Acute Disease↗

PubMed1991

5-aminosalicylic acid in the prevention of relapses of Crohn's disease in remission: a long-term study.

The aim of the study was to evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in maintaining the remission in patients with inactive Crohn's disease over a period of three years, using either the Crohn's Disease Activity Index (CDAI) and or the Laboratory Index (LI). Thirty-eight patients entered in the study; 20 received 5-ASA 1.6 g/day and 18 no specific therapy. The patients were followed for three years. Of the patients, 86% presented a relapse, 80% in the 5-ASA group and 94% in the control group. Two patients requested surgical therapy. All patients with clinical relapse had CDAI greater than 150 and LI greater than 100. 5-Aminosalicylic acid was well tolerated and was able to protect from relapse up to 60% of the patients in the first year of therapy. When treatment with 5-ASA is prolonged for periods longer than one year a progressive increase in the number of patients who present relapse can be observed, but of the 5-ASA group, 80% of relapses occurred in the three years whereas the control group showed 94% relapses at the end of the first year.

Adult↗

PubMed1990

[Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival].

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.

Adult↗

PubMed1988

Long-term follow-up after relapses in children with Hodgkin's disease.

In the years 1969-1980, 68 children with Hodgkin's disease were subjected to a combined MVPP and radiotherapy. Remissions were obtained in 64 patients, and relapses occurred in 11 children. The treatment of relapse consisted in administration of B-DOPA alone or alternatively with MVPP combined with radiotherapy (in 7 out of 11 patients). The patients were recycled every 2-3 weeks which, with other modifications of chemotherapy, allowed for the completion of the six first cycles within the period of 4,5 to 7 months. A relapse caused death of one child, and two others demonstrated further relapses. At present eight children have been showing disease-free survival following a relapse for the period of 29+ to 152+ (median, 94.5 months). The authors concluded that in patients with relapses of Hodgkin's disease the decisive role rests upon aggressive chemotherapy (high frequency of cycles).

Adolescent↗

PubMedDate not supplied

Isolated testicular relapse in a boy with acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

About 5-10% of boys with acute lymphoblastic leukemia (ALL) present with isolated testicular relapse. Very frequently these relapses occur during treatment or in the following six months, and in these cases the prognosis is very severe. The patients are usually treated with radiotherapy and chemotherapy or bone marrow transplantation (BMT). Testicular relapses after BMT are relatively rare. We report the case of a child with ALL who presented testicular relapse during therapy and was treated with local radiotherapy (2000 cGy), chemotherapy and allogeneic matched BMT. The preparative regimen consisted of Cyclophosphamide (60 mg/kg/day x 2 days) and total body irradiation (200 cGy x 2/day x 3 days). Engraftment was documented at day + 14. The patient presented again with testicular relapse at day + 146, and was therefore treated with orchiectomy, local radiotherapy and systemic chemotherapy. A marrow relapse followed, however, at day + 284 and the patient died of progressive disease.

Bone Marrow Transplantation↗