Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case.

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare and challenging complication associated with poor prognosis and limited treatment options. Emerging T-cell directing therapies, such as bispecific antibodies (bsAbs) and chimeric antigen receptor T cells (CAR-T), have shown remarkable success in treating MM, but their efficacy in CNS involvement remains unclear. Elranatamab, a humanized bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3-expressing T cells, has demonstrated promising results in relapsed refractory MM. However, its efficacy in treating CNS-MM has not been reported. We present a case of a 37-year-old male MM patient with CNS involvement who has been successfully treated with Elranatamab.

Survival outcomes of hypomethylating agents maintenance therapy in new diagnosed AML patients: Real experience data.

OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy that frequently affects elderly population. With introducing the hypomethylating agents (HMAs) in elderly AML treatment, survival rates and quality of life have improved. However, long-term management in elderly and frail patients is still a challenge. In the present study, we aimed to determine whether HMA maintenance therapy is required until disease progression in frail and elderly AML patients by examining with a real-life data. METHODS: In a multicenter study, we analyzed non-promyelocytic elderly AML patients who were treated with first-line azacitidine or decitabine monotherapy in two different groups, retrospectively. While patients were treated with HMA until progression in the maintenance group, 6+3 cycles of azacitidine or decitabine were administered as a standard care of elderly AML patients in the non-maintenance group. Survival outcomes were compared between the groups. RESULTS: HMA therapy was maintained until progression in 20 patients, and HMA therapy was terminated after 6+3 cycles in 21 patients. Patients received a median of 6 (1-14) HMA cycles during follow-up time. The median 7.5 months of overall survival were observed (2-17 months) in maintenance and 3 months (1-13 months) in non-maintenance groups (p=0.001). CONCLUSION: Despite long-term exposure to HMA may appear as a risk factor for complications and toxicities in elderly and frail AML patients, the maintenance of therapy until disease progression provides a significant survival advantage. Therefore, we suggest that HMA therapy should continue until disease progression regardless the sort of HMA.

Castleman Disease: A Multicenter Case Series from Turkey

Objective: Castleman disease (CD) is a rare disease also known as angiofollicular lymph node hyperplasia. The two main histological subtypes are the hyaline vascular and plasma cell variants. It is further classified as unicentric CD (UCD) or multicentric CD (MCD) according to the anatomical distribution of the disease and the number of lymph nodes involved. The aim of this multicenter study was to evaluate all cases of CD identified to date in Turkey to set up a national registry to improve the early recognition, treatment, and follow-up of CD. Materials and Methods: Both adult (n=130) and pediatric (n=10) patients with lymph node or involved field biopsy results reported as CD were included in the study. Patients' demographic information, clinical and laboratory characteristics, imaging study results, treatment strategies, and clinical outcomes were evaluated retrospectively. Results: A total of 140 patients (69 male and 71 female) with a diagnosis of UCD (n=73) or MCD (n=67) were included. The mean age was 39 years in the UCD group and 47 years in the MCD group. Female patients were more common in the UCD group. The most common histological subtype was hyaline vascular for both UCD and MCD patients. Asymptomatic patients were more common in the UCD group. Anemia, elevations of acute phase reactants, and hypoalbuminemia were more common in the MCD group. The most commonly used treatment strategies for UCD were surgical excision, rituximab, and radiotherapy, respectively. All UCD patients were alive at a median of 19.5 months of follow-up. The most commonly used treatment strategies for MCD were methyl prednisolone, R-CHOP, R-CVP, and rituximab. Thirteen MCD patients had died at a median of 34 months of follow-up. Conclusion: This study is important in presenting the patient characteristics and treatment strategies for CD from Turkey, with the potential of increasing awareness about CD. Treatment data may help in making decisions, particularly in countries that do not have access to siltuximab. However, larger prospective studies are needed to make definitive conclusions.

A rare case of pulmonary lymphomatoid granulomatosis complicated with venous thrombosis.

Lymphomatoid granulomatosis (LG) is Epstein-Barr virus associated and aggressive B cell lymphoproliferative disease. The most common sites of involvement are lungs, skin, kidneys, liver and central nervous system. The clinical presentation of pulmonary LG may mimic infectious diseases, malignancies or vasculitis. While treatment approach of low grade disease is watch and wait, patients with advanced stage require aggressive treatment with chemotherapy. Patients with hematological malignancy as well as solid tumors are at increased risk of venous thromboembolic events (VTE). We reported here in a case of pulmonary LG who was complicated with VTE during treatment with chemo-immunotherapy After 4 cycles of R-CHOP, she achieved complete remission for LG and was followed up without relapse for 2 years. She was anticoagulated with Low-Molecular-Weight Heparin (LMWH) during chemotherapy period, and the thrombus improved over the next several weeks. While on this paper written, patient completed her pregnancy successfully under anticoagulation prophylaxis.

The outcome of COVID-19 in patients with hematological malignancy.

Objective: The aim of this study was to examine the effect of coronavirus disease 2019 (COVID-19) on the malignancy-related clinical course and overall survival, and to determine the factors affecting mortality. Methods: This retrospective study included 77 patients with hematological cancer and COVID-19. Patients were sub-grouped for analysis as survivors and non-survivors. Results: COVID-19 was seen more frequently in myeloproliferative neoplasms (MPN), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. Mortality rate due to COVID-19 was 20.8%. No statistically significant difference was determined between the survivor and non-survivor groups with respect to age and gender, presence of any comorbidity, leukocyte, neutrophil, lymphocyte, and monocyte values. Platelet count and hemoglobin count were significantly lower in the group with mortality than in the group with recovery. Conclusion: It should be kept in mind that low hemoglobin and platelet levels contribute to mortality. In addition, it is important to protect patients with hematological cancer from COVID-19 and undertake effective vaccination due to its mortal course.

Vitreous hemorrhage: A rare ophthalmic adverse effect due to imatinib treatment.

INTRODUCTION: Imatinib is generally well tolerated by patients. The most common ophthalmic side effects are eyelid edema and periorbital edema. Other side effects which occur at rates of <1% include blepharitis, blurred vision, conjunctival hemorrhage, conjunctivitis, retinal hemorrhage, etc. An uncommon case is here reported of a 51-year-old male with chronic myeloid leukemia who developed vitreous hemorrhage due to imatinib after 9 months of treatment. CASE REPORT: A 51-year-old male with leukocytosis detected in the blood test examination was referred to the Hematology Department. The bone marrow biopsy result was compatible with chronic myeloid leukemia. Imatinib treatment (400 mg/day) was started. In the ninth month of imatinib treatment, the patient complained of a sudden decrease in vision. Vitreous hemorrhage was detected in the left eye and the patient underwent surgery. Vitreous hemorrhage recurred 1 month after the operation. On the fourth day after the discontinuation of imatinib treatment, the patient's ophthalmic complaints improved significantly. The Naranjo algorithm was applied and a score of 9 was detected. The vitreous hemorrhage of the patient was attributed to imatinib, and so the treatment of the patient was switched to bosutinib. DISCUSSION: Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). The conjunctiva and sclera have a large amount of c-kit positive mast cells which are inhibited by imatinib. The inhibition of c-kit positive mast cells by imatinib may be responsible for further exposure of the conjunctival mucosa to injuries.

A Real-life Turkish Experience of Venetoclax Treatment in High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia.

INTRODUCTION: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. MATERIALS AND METHODS: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. RESULTS: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. CONCLUSION: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case.

INTRODUCTION: All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. CASE REPORT: A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. MANAGEMENT & OUTCOME: Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. DISCUSSION: This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

Synchronous detection of multiple myeloma and acute myeloid leukemia: A diagnostic and therapeutic challenge.

INTRODUCTION: Synchronous detection of multiple myeloma and acute myeloid leukemia in a single patient is a rare coincidence. Treatment of these patients is still unclear, mostly based on acute myeloid leukemia strategies combined with bortezomib. CASE REPORT: A 72-year-old male with no medical history was investigated for pancytopenia. On medical examination, he was complicated with a wide and severe skin infection on arm. On examination of bone marrow aspirate, 25% myeloblasts infiltration and additional 10% plasma cells were seen. Acute myeloid leukemia was diagnosed and plasma cell proliferation was attributed to reactive plasmacytosis due to skin infection. However, flowcytometric studies and immunohistochemical examination revealed two different cell populations with 30-40% atypical plasma cells and >20% myeloblasts. Serum M-protein detected by serum electrophoresis test and immunofixation test revealed a monoclonal IgG lambda band. He was diagnosed with concurrent acute myeloid leukemia and multiple myeloma without history of chemotherapy.Management and outcome: The patient was initially treated with bortezomib and dexamethasone for the myeloma. Subsequently, azacitidine was administered subcutaneously for the acute myeloid leukemia treatment. The tru-cut biopsy of the lesion on his arm revealed suppurative inflammatory findings and no malign cells detected. Antibiotherapy was started according to susceptibility. He expired after three months of survival. DISCUSSION: The synchronous occurrence of these two different clonal hematological malignancies is rare in hematology practice. Patient-based prospective studies and case series are needed to guide diagnosis and treatment strategies. Furthermore, this report highlights the importance of ruling out reactive plasmacytosis in patients with hematological malignancy who developed severe infections.

A rare case of diffuse large B-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. Herein, we aimed to report a diffuse large B-cell lymphoma (DLBCL) case that was presented as HLH. CASE REPORT: A 32-year-old man presented to a hospital with complaints of vomiting, nausea and diarrhea in October 2019. Fever and hepatosplenomegaly was detected in physical investigation. Bone marrow aspiration investigation revealed the hemaphagocytosis. HLH-2004 protocol was started for hemophagocytosis. Whole body magnetic resonance imaging (MR) revealed no lymphadenopathy. Bone marrow biopsy revealed high-grade B-cell lymphoma, favoring DLBCL. There were no pathologic cells in lumber puncture investigation. MANAGEMENT AND OUTCOME: He was diagnosed with secondary hemaphagocytic syndrome due to DLBCL, and chemotherapy was switched to rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-EPOCH) regimen. After three cycles of R-EPOCH chemotherapy regimen, complete remission was confirmed with positron emission tomography-computerised tomography (PET-CT) scan. DISCUSSION: Our patients' findings are suitable for six out of eight criteria of hemaphagocytic syndrome. The H-score of our patient was more than 250, reflecting the >99% probability of HLH syndrome. Compatible with literature knowledge, our patient had responded very well to etoposide-containing regimens. In our patient, no lymphadenopathy was detected by physical examination or MR scan, and the diagnosis of DLBCL was only made by the result of bone marrow investigation. In conclusion, herein, we have reported a DLBCL case that had presented with HLH, and clinicians should be aware that B-cell lymphomas may be the underlying cause of HLH.

Prognostic Value of Baseline Serum Lactate Dehydrogenase Level in Patients With Hairy Cell Leukemia.

BACKGROUND: Hairy cell leukemia is a rare B-cell lymphoproliferative disorder. It has an indolent course with relapse and remission periods. The aim of this study was to investigate the clinical characteristics and risk factors affecting the outcome of patients with hairy cell leukemia. PATIENTS AND METHODS: The retrospective data of 65 patients were evaluated according to initial hematologic and biochemical parameters, response rates, progression-free survival, and overall survival. Factors effecting response and survival rates were analyzed. RESULTS: The median follow-up duration was 62.8 months (range, 5.7-229.3 months). The result of the analysis showed that the patients with relapse/progressive disease had higher lactate dehydrogenase (LDH) levels at the time of diagnosis than patients without relapse/progression (median [range], 243 [137-540] vs. 179 [99-334] U/L, P = .01). Patients with LDH ≥ 200.5 IU at the time of diagnosis were demonstrated to have a shorter progression-free survival than those with LDH < 200.5 IU (P = .010). CONCLUSION: Serum LDH level is significantly associated with relapse/progression in hairy cell leukemia patients. Patients with higher LDH levels at diagnosis should be monitored closely even if they experience complete remission.

Diffuse large B cell lymphoma progression with skin involvement: A case report.

Diffuse large B cell lymphoma (DLBCL) constitutes the most frequent subtype of all non-Hodgkin's lymphomas. DLBCL is an aggressive disease and extranodal involvement is seen in approximately 30% of patients and most common extranodal sites are gastointestinal tract and skin. Skin involvement may be either primary or secondary. Secondary cutaneous lymphoma has a worse prognosis. The case is here reported of a 56-year old male DLBCL patient with cutaneous lesions and aggressive clinical course. The patient had no skin lesions at diagnosis and during follow up and treatment period, skin, cerebrospinal fluid and bone marrow involvement was occurred. Salvage chemotherapy and autologous stem cell transplantation was planned but the patient died before the second cycle of salvage chemotherapy. In contrast to primary cutaneous lymphoma, which tends to be more indolent, secondary skin involvement is associated with unfavourable prognosis. In conclusion it should be kept in mind that skin can be involved in lymphoma patients and in these cases, skin biopsy should be performed rapidly.

Q fever as a rare cause of hemophagocytic lymphohistiocytosis: Case report.

Hemophagocytic Lymphohistiocytosis (HLH) is a reactive disorder of the mononuclear phagocytic system characterized by increased histiocytic proliferation, activation and hemaphagocytosis. The underlying etiology may be genetic (primary) or acquired (secondary). Secondary causes include drugs, autoimmune diseases, malignancies and infections of which EBV is the most common. A 28-year old male patient who was a shepherd with no known concomitant comorbid disease was admitted to the Emergency Department with the complaints of abdominal pain, fever, severe fatigue. Physical examination revealed high fever, hepatosplenomegaly and laboratory examination revealed pancytopenia, hyperferritinemia and hypertriglyceridemia. Hemophagocytes were observed in the bone marrow biopsy and the patient was diagnosed as HLH. The patient was treated with cyclosporine A, dexamethasone, intravenous immunoglobulin (IvIg) and etoposide according to the HLH 2004 protocol. Coxiella burnetii was detected in the serological evaluation of the etiology and doxycycline was added to the current treatment. Fever was controlled in the second week of the treatment and the patient was discharged after complete recovery of the cytopenia in the fourth week. In the outpatient setting, treatment was completed in 8 weeks and follow-up of the patient is still ongoing without medication. To the best of our knowledge, this is the first case from Turkey of HLH secondary to Q-fever which was treated and managed successfully. Since the mortality of HLH is quite high, the etiology should be determined as soon as possible to be able to provide appropriate treatment.

R-IDARAM treatment in central nervous system lymphomas: A single-center experience and review of the literature.

INTRODUCTION: Central nervous system lymphomas (CNSLs) require effective treatment strategies due to aggressive nature of disease. Despite therapeutic approaches having improved in the last decades, there is no standard treatment for these patients. As a CNSL targeted-therapy IDARAM protocol was developed, the outcomes were reported with a few studies. We observed the R-IDARAM protocol in our CNSL cases, and we discuss the effectiveness, tolerability, and toxicity with a review of the literature in this article. SUBJECTS AND METHODS: We retrospectively analyzed response rates, progression-free survival, adverse events, and long-term side effects in patients who were treated by modified R-IDARAM as standard clinical care of CNSL in our hematology department. RESULTS: Response was achieved in five of nine patients. Three patients (two primary CNSL and one secondary CNSL) are still being followed up without disease progression with a median duration of follow-up of 79 months (88, 79, and 17 months, respectively). Manageable hematological side effects including thrombocytopenia and neutropenia were experienced by all patients. CONCLUSION: R-IDARAM protocol may be an option with high early response rates and manageable toxicity. Hematological side effects are the main problem, and long-term neurological toxicity is not common. Eligible patients must continue with autologous stem cell transplantation due to poor long-term survival outcomes.

The incidence and risk factors of thrombosis and the need for thromboprophylaxis in lymphoma and leukemia patients: A 9-year single-center experience.

BACKGROUND: Patients with cancer are at increased risk of thromboembolic complications. There is no evidence-based guideline on the use of routine prophylaxis in hematological malignancies except in patients with multiple myeloma. The purpose of this study was to determine the incidence and risk factors of thrombosis and suggest a rationale for primary thromboprophylaxis in acute leukemia and lymphoma patients. PATIENTS AND METHODS: A retrospective study was conducted on newly-diagnosed acute leukemia and lymphoma patients who presented at our institution from November 2009 to March 2018. The study included a total of 157 patients with acute leukemia and 238 patients with lymphoma. The groups were analyzed to determine the incidence and risk factors of thromboembolic complications. RESULTS: The incidence of all thrombotic complications was 10.12% (40/395) including 11.4% (18/157) in patients with acute leukemia and 9.2% (22/238) in patients with lymphoma. The majority of events occurred in the first 6 months. Acute leukemia patients with thrombosis had a higher number of comorbidities than those without thrombosis (p < 0.05). Lymphoma patients with thrombotic complications had significantly higher beta-2-microglobulin and lactate dehydrogenase levels compared to those without thrombosis (p < 0.05). Major bleeding events developed in five (3.1%) acute leukemia patients and two (0.8%) lymphoma patients. All the major bleeding events occurred when the patients were thrombocytopenic (platelet < 50,000/mm3). CONCLUSIONS: Acute leukemia patients with any comorbidity and lymphoma patients with higher lactate dehydrogenase and beta-2-microglobulin are at high risk of developing thromboembolic complications. The prophylactic use of anticoagulant should be considered for those patients especially in the first 6 months.

Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib.

INTRODUCTION: Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib. CASE REPORT: A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE). MANAGEMENT AND OUTCOME: Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse. DISCUSSION: Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.

An acute transverse myelitis attack after autologous stem cell transplantation: A rare case.

Transverse myelitis is a quite rare complication of hematopoietic stem cell transplantation. The case is here reported of a 49 year old male with diffuse large B cell lymphoma in complete remission who developed transverse myelitis after autologous stem cell transplantation. The patient presented with numbness and sensory loss of the bilateral lower extremities and difficulty in urinating on the 20th day after cell transplantation. Millimetric hyperintensity was detected in the C5-C6 and T2-T5 segments of the spinal cord on cervical and thoracic vertebral magnetic resonance imaging. Treatment was initiated of pulse steroid and intravenous immunoglubulin followed by plasmapheresis and cyclophosphamide due to inadequate response. The patient then started a rehabilitation program and was discharged in the 9th month after stem cell transplantation when most of the symptoms were relieved. To the best of our knowledge, this is the first case reported in literature of TM development after autologous stem cell transplantation.